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[(work)-416.7(in)-416.4(additional)-418.9(model)-414.2(systems)-417.1(to)-415.4(understand)-422.2(the)-416(contexts)]TJ 0 -1.2055 TD [(in)-303(which)-300.3(stimulation)-303.7(strength)-302.6(impacts)-302.5(dif)56.5(ferentiation)-305.3(outcome.)]TJ 1.2651 -1.2114 TD [(The)-247.2(predicted)-252.4(consequence)-255.2(of)-247.4(dif)62.5(ferentiation)-251.6(biases)-254.9(driven)-251.8(by)]TJ -1.2651 -1.2114 TD [(stim)-10.5(ulati)-9.4(on)-504.6(st)-8.3(reng)-11.3(th)-503.8(wou)-9.8(ld)-501.1(b)-7.2(e)-503(a)-505.9(pool)-509.7(of)-504(me)-7.3(mory)-509.7(cell)-10.7(s)-501.3(wit)-8.2(h)]TJ T* [(greater)-382(TCR)-383.7(diversity)-381.5(and,)-384.6(on)-379.3(average,)-382.6(lower)-383(antigenic)-379.3(af)]TJ /F7 1 Tf 23.5663 0 TD ()Tj /F6 1 Tf 0.5311 0 TD (nity)Tj -24.0974 -1.2114 TD [(than)-253.8(the)-254.9(pool)-253(of)-259.3(ef)62.5(fector)-253.2(cells.)-258.2(Evidence)-260.2(of)-253.3(this)-255.7(phenomenon)-255.8(was)]TJ T* [(observed)-269.4(in)-261.2(murine)-267.8(models)-265.1(of)-265.3(in)]TJ /F7 1 Tf 13.0334 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(uenza)-265.9(infection)-268.4(\()]TJ 0 0 0 0.7 k 6.7375 0 TD (28)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.4774 0 TD (37)Tj 0 0 0 1 k 0.9608 0 TD [(\),)-262.5(while)]TJ -22.701 -1.2114 TD [(similar)-451.7(results)-457.5(were)-448.4(reported)-459.1(in)-452.2(CD4)]TJ 7.1249 0 0 6.3326 192.9259 289.1905 Tm (+)Tj 9.5 0 0 9.5 201.2598 284.9385 Tm [(T)-454.2(cells)-452.4(during)-452.1(murine)]TJ -16.4111 -1.2055 TD 0.013 Tc [(ly)5.5(mph)13(o)-6.3(cy)5.5(ti)4.5(c)-513.9(c)5.3(hori)4.5(omen)5(in)5(gi)4.5(ti)4.5(s)-512.2(v)-0.4(i)4.5(r)1(us)-512.2(\(LCMV\))-509.3(i)4.5(n)-1(fe)5.3(cti)4.5(o)-0.2(n)-508.2(\()]TJ 0 0 0 0.7 k 24.1034 0 TD 0.0163 Tc (38)Tj 0 0 0 1 k 0.9847 0 TD 0.0091 Tc (\).)Tj -25.088 -1.2114 TD 0 Tc [(Interestingly,)-458.2(this)-452.7(latter)-447.4(study)-455.8(highlighted)-454.1(dif)62.5(ferences)-458.1(between)]TJ T* [(TCR-ligand)-291(af)]TJ /F7 1 Tf 5.6633 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-289(and)-286.3(tetramer)-292.9(avidity)-288.8(measurements,)-296(serving)]TJ -6.1944 -1.2114 TD [(as)-410.4(a)-416.4(reminder)-412.8(that)-415.2(additional)-413(factors)-417.3(such)-412.8(as)-410.4(TCR)-413.6(expression)]TJ T* 0.014 Tc [(levels)-511.2(must)-513.5(be)-518.9(considered)-516.3(when)-513.2(comparing)-512.7(l)1.4(igand)-516.3(b)0.8(i)5.5(n)-6(ding)]TJ T* 0 Tc [(tendencies)-349.4(between)-342.4(populations)-352.6(\()]TJ 0 0 0 0.7 k 13.5585 0 TD (38)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-340.1(Furthermore,)-354.2(exploration)]TJ -14.5193 -1.2055 TD [(of)-330.9(a)-326.9(broader)-330.4(range)-332.2(of)-325(infections)-334.1(in)-326.9(murine)-333.4(and)-328.1(human)-327.8(systems)]TJ 0 -1.2114 TD [(will)-365.2(be)-361.1(important)-366.2(to)-361.7(understand)-368.5(the)-362.3(generalizability)-372.4(of)-360.8(antigen)]TJ T* 0.0404 Tc (af)Tj /F7 1 Tf 0.74 0 TD 0 Tc ()Tj /F6 1 Tf 0.5729 0 TD 0.0379 Tc [(nity)-536.5(dif)60.4(f)0.7(erences)-541(between)-543(T)-535.7(c)0.4(e)-5.6(l)1.5(l)-535.6(s)-3.9(ub)-5.2(sets.)-537.8(N)1.1(ev)-5.4(ertheless,)]TJ -1.3129 -1.2114 TD 0.0577 Tc [(observations)-557(of)-558.4(greater)-557(T)-2.6(C)3.5(R)-557.6(diversity)-558.5(within)-559(memory)]TJ T* 0 Tc [(populations)-316.8(lead)-316.5(to)-314(the)-314.5(intriguing)-320.8(hypothesis)-319.3(that)-313.8(this)-315.4(serves)-321.4(as)]TJ T* 0.0274 Tc [(a)-496.4(m)-2(e)-4.2(c)1.8(han)-4.5(i)1(sm)-497.4(to)-499(protec)-4.2(t)-500.1(a)-1.1(gai)-5(n)1.5(st)-500.1(re)-4.2(in)-4.5(fe)-4.2(ct)-4.8(ion)-499.8(w)0.2(ith)-503.8(m)3.9(ut)-4.8(ate)-4.2(d)]TJ T* [(pathogens.)-494.6(In)-499.8(s)3.5(upport)-494.1(of)-499.2(this)-497.8(hy)]TJ 14.7043 0 TD 0.028 Tc [(pothes)4.1(is)4.1(,)-500(r)4.1(educing)-492.7(c)2.4(lonal)]TJ -14.7043 -1.2055 TD 0.0424 Tc [(div)5.1(e)-1.1(rsity)-514.1(of)-508(th)6.5(e)-514.3(m)1(emo)5.3(r)-5.4(y)-508.1(p)1.4(ool)-507.3(by)-508.1(deletin)4.5(g)]TJ /F11 1 Tf 19.6933 0 TD 0.0443 Tc [(Cd)7.2(27)]TJ /F6 1 Tf 2.7392 0 TD 0 Tc (\()Tj 0 0 0 0.7 k 0.3819 0 TD 0.0462 Tc (37)Tj 0 0 0 1 k 1.0443 0 TD 0.5521 Tc [(\)o)509(r)]TJ -23.8587 -1.2114 TD 0 Tc [(interrupting)-421.5(EOMES/BLC2)-419.4(signaling)-423.4(\()]TJ 0 0 0 0.7 k 15.8083 0 TD (28)Tj 0 0 0 1 k 0.9608 0 TD [(\))-414.9(impaired)-421.3(protection)]TJ -16.7691 -1.2114 TD [(against)-435.5(mutated)-432.7(pathogen)-436.6(variants)-435.5(while)-438.1(leaving)-432.4(robust)-433.8(recall)]TJ T* [(responses)-250.8(to)-242.3(the)-242.9(original)-248(pathogen.)-248.4(Thus,)-247.5(mechanisms)-250.8(that)-242.2(drive)]TJ T* [(dif)62.5(ferences)-177.6(in)-177.7(TCR)-168.9(af)]TJ /F7 1 Tf 8.11 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-175.6(and)-172.9(heterogeneity)-181.9(between)-175.4(ef)62.5(fector)-175.7(and)]TJ 18.8101 66.5811 TD [(memory)-200.7(cells)-201.7(may)-196.7(have)-204.9(been)-197.8(naturally)-200.6(selected)-206.1(for)-199.7(their)-197.8(ef)]TJ /F7 1 Tf 22.6174 0 TD ()Tj /F6 1 Tf 0.5311 0 TD (ciency)Tj -23.1485 -1.2114 TD (in)Tj /F7 1 Tf 0.9787 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(ghting)-177.2(both)-178.1(current)-180.2(and)-178.9(future)-182.9(infections.)-181.8(It)-176.6(will)-174.3(be)-176.1(interesting)]TJ -1.5098 -1.2114 TD [(to)-272.2(see)-272(whether)-272(future)-272.5(studies)-273.6(support)-275.8(or)-269.9(contradict)-274.5(this)-267.7(theory.)]TJ 1.2651 -1.2114 TD [(Ch)-6.5(ro)-13.2(ni)-10.6(c)-509(a)0(n)-12.6(t)0(i)-10.9(g)0(e)-9.2(n)-509.3(pr)-11.2(e)-7.7(s)0(e)-7.7(n)-8(c)-7.7(e)-509(ca)-12.3(n)-509.3(f)0(u)-12.5(r)0(t)-8.4(h)0(e)-7.8(r)-513.2(dr)-11.2(iv)-10.1(e)-509(C)-6.4(D8)]TJ 7.1249 0 0 6.3326 517.4928 680.2014 Tm (+)Tj 9.5 0 0 9.5 526.4503 675.9495 Tm [(T)-507.9(c)-7.7(el)-8.3(l)]TJ -23.1903 -1.2114 TD 0.0377 Tc [(dif)60.2(f)0.5(erentiation.)-532(In)-537.3(certain)-531.3(contexts,)-538(s)1.9(uch)-535.3(a)-2.7(s)-535.2(l)1.3(aten)5.8(t)-537.5(C)1.4(MV)]TJ T* 0.031 Tc [(i)4.5(n)-0.9(fe)5.4(ct)4.8(io)5.8(n,)-526.8(C)6.7(T)0.5(Ls)-524(wi)4.5(t)4.8(h)-530.1(an)-526(ef)65.4(f)5.7(ect)4.8(or)-524(memo)5.8(ry)-525.5(phen)5.1(ot)4.8(ype)-525.7(a)2.5(nd)]TJ 0 -1.2055 TD 0 Tc [(persistent)-429.8(ef)56.5(fector)-426.3(functionality)-436.1(gradually)-429.7(expand)-433.9(in)-428.3(a)-428.3(process)]TJ 0 -1.2114 TD [(that)-260.1(has)-261.4(been)-263.4(termed)-261.3(memory)-260.4(in)]TJ /F7 1 Tf 13.0811 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(ation)-257.6(\()]TJ 0 0 0 0.7 k 2.6437 0 TD (14)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-256.6(Interestingly,)-267.3(while)]TJ -17.2167 -1.2114 TD [(C)-6.4(T)-6.6(L)-513.3(e)-7.7(xp)-8.6(a)-10.6(n)0(s)-14(i)0(o)-9.8(n)-515.3(co)-9(rr)-12(e)-7.7(l)-6.6(at)-12.9(e)-7.7(s)-513.2(wi)-11.9(t)-8.3(h)-507.4(T)-6.6(C)-6.4(R)-6.6(-)-10(l)-6.6(i)0(g)-10.1(a)0(n)-12.6(d)-512.4(a)-10.6(f)]TJ /F7 1 Tf 19.5918 0 TD ()Tj /F6 1 Tf 0.5371 0 TD [(n)-8(i)0(t)-10.9(y)-514.7(in)-517.9(ac)-12.3(ut)-13.5(e)]TJ -20.1289 -1.2114 TD [(infection)-363.9(\()]TJ 0 0 0 0.7 k 4.237 0 TD (39)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.5789 0 TD (40)Tj 0 0 0 1 k 0.9608 0 TD [(\),)-364(this)-357.2(relationship)-369.3(appears)-361.5(to)-361.7(shift)-364.6(with)-360.5(latent)]TJ -6.7315 -1.2114 TD [(infection.)-307.1(Using)-303.6(a)-303(model)-300.8(of)-301.1(murine)-309.6(CMV,)-301.1(a)-303(recent)-302.1(study)-306.6(found)]TJ T* [(that)-361.5(while)-360.5(high)-362.4(af)]TJ /F7 1 Tf 7.2388 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-360.6(CTLs)-359.3(dominated)-370.7(early)-360.6(in)-362.7(the)-362.3(response,)]TJ -7.7699 -1.2055 TD [(lower)-275.6(af)]TJ /F7 1 Tf 3.1509 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-277(cells)-273.3(became)-279.3(most)-277.8(abundant)-277.9(over)-273.1(time)-280.8(\()]TJ 0 0 0 0.7 k 17.8373 0 TD (41)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-274.5(These)]TJ /F7 1 Tf -22.4802 -1.2114 TD ()Tj /F6 1 Tf 0.5311 0 TD [(ndings)-258.1(were)-251.5(corroborated)-253.6(by)-253.4(measuring)-256(the)-254.9(af)]TJ /F7 1 Tf 18.3147 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nities)-256(of)-247.4(human)]TJ -19.377 -1.2114 TD (CD8)Tj 7.1249 0 0 6.3326 323.8298 553.6628 Tm (+)Tj 9.5 0 0 9.5 331.0298 549.4676 Tm [(T)-322.9(cells)-321.1(speci)]TJ /F7 1 Tf 4.9353 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(c)-324(for)-325(CMV-derived)-326.2(ligands,)-329.7(where)-323.2(in)]TJ /F7 1 Tf 15.0027 0 TD ()Tj /F6 1 Tf 0.5311 0 TD (ation)Tj -23.62 -1.2114 TD [(of)-509.9(th)-8.4(e)-509(m)0(e)-7.3(m)0(o)-6.9(r)0(y)-514.8(pop)-11.6(ula)-10.4(tio)-12.2(n)-503.3(w)-9.3(as)-505.9(i)-8.5(nve)-11.3(rse)-13.7(ly)-509.4(co)-9(rre)-13.7(lat)-7.6(e)-7.7(d)-506.4(wit)-8.2(h)-507.4(i)-8.5(ts)]TJ T* [(ligand)-446.2(af)]TJ /F7 1 Tf 3.5746 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-444.1(\()]TJ 0 0 0 0.7 k 2.3513 0 TD (41)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-441.6(The)-444.1(mechanisms)-447.8(underlying)-446.2(the)-439.8(in)]TJ /F7 1 Tf 15.677 0 TD ()Tj /F6 1 Tf 0.5311 0 TD (ation)Tj -23.62 -1.2114 TD 0.019 Tc [(of)-513.5(low)-515.4(a)-3.5(f)]TJ /F7 1 Tf 4.0461 0 TD 0 Tc ()Tj /F6 1 Tf 0.549 0 TD 0.0185 Tc [(nity)-514.1(p)-4.6(o)-0.7(pulations)-518.6(during)-514.1(C)0.2(MV)-513.8(infection)-520.6(a)2(re)-520.3(not)]TJ -4.5951 -1.2055 TD 0.0129 Tc [(c)5.2(o)-0.3(mp)12.9(le)5.2(te)5.2(l)6.3(y)-507.8(re)5.2(sol)6.3(v)5.4(ed,)-503.1(b)-0.3(ut)-502.7(ev)5.4(i)4.4(d)1.8(en)4.9(ce)-502(sug)5.4(g)-0.5(e)5.2(s)0.9(t)4.6(s)-506.3(t)4.6(h)0.8(at)-508.6(t)4.6(h)0.8(e)5.2(y)-507.8(r)12.9(e)]TJ /F7 1 Tf 23.9661 0 TD 0 Tc ()Tj /F6 1 Tf 0.5431 0 TD 0.0077 Tc (ect)Tj -24.5092 -1.2114 TD 0 Tc [(early)-318.8(dif)62.5(ferentiation)-317.2(divergence)-324.2(that)-313.8(impacts)-320.4(the)-314.5(long-term)-317.6(self-)]TJ T* [(re)-13.7(n)-8(e)-7.7(wi)-11.9(n)-8(g)-508.8(p)-11.1(o)-7.3(te)-10.1(n)-8(t)-8.3(ia)-13.2(l)-513.9(o)0(f)-515.9(e)-7.7(a)-10.6(c)0(h)-515.1(c)-7.7(l)-6.6(o)-7.3(n)-8(e)-7.7(.)-510.1(S)-9.4(pe)-12.9(c)-7.7(i)]TJ /F7 1 Tf 16.978 0 TD ()Tj /F6 1 Tf 0.5371 0 TD [(c)-7.7(a)0(l)-11.2(l)-6.6(y)-7.5(,)-510.1(f)-7.4(a)-10.6(te)-517.3(ma)-16.2(pp)-10.3(i)-8.5(n)-8(g)]TJ -17.5151 -1.2114 TD [(experiments)-456.1(tracking)-450.9(the)-451.8(progeny)-448.9(of)-450.3(individual)-455.7(nave)-448.1(murine)]TJ T* 0.0087 Tc (CD8)Tj 7.1249 0 0 6.3326 324.0566 461.707 Tm 0 Tc (+)Tj 9.5 0 0 9.5 333.0708 457.455 Tm 0.0087 Tc [(T)-505.2(cells)-504.5(sh)8.7(o)-4.6(w)-0.6(ed)-503.7(tha)8.7(t)-511.5(potential)-505.2(f)1.3(or)-510.5(long-ter)8.7(m)-516.1(m)8.7(e)-4.6(m)-2.8(or)8.7(y)]TJ -2.8346 -1.2114 TD 0.0324 Tc (in)Tj /F7 1 Tf 0.8593 0 TD 0 Tc ()Tj /F6 1 Tf 0.561 0 TD 0.0312 Tc [(at)5(ion)-525.8(w)-2(as)-529.8(det)5(e)-0.4(rmined)-528.9(w)4(i)-1.2(t)5(h)1.2(in)-531.8(6)-528.2(d)2.2(ays)-529.8(o)0.1(f)-525.2(i)-1.2(nfe)5.6(c)-0.4(ti)4.7(on)-531.8(and)]TJ -1.4203 -1.2114 TD 0 Tc [(correlated)-496.7(with)-497.7(a)-494(central)-496.5(memory)-499.1(precursor)-498.6(phenotype)-504.5(\()]TJ 0 0 0 0.7 k 24.1392 0 TD (42)Tj 0 0 0 1 k 0.9608 0 TD (\).)Tj -25.1 -1.2055 TD [(Transcriptomic)-251.2(pro)]TJ /F7 1 Tf 7.8057 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(ling)-239.5(of)-247.4(high-af)]TJ /F7 1 Tf 5.5857 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-241.2(CTLs)-245.9(shortly)-244.7(before)-246.2(the)]TJ -14.4537 -1.2114 TD [(point)-371.5(at)-365(which)-371.9(they)-369.7(lost)-368.3(dominance)-378.9(in)-368.7(murine)-369.2(CMV)-369.9(infection)]TJ T* [(revealed)-470.7(upregulation)-467.9(of)-468.2(co-inhibitory)-471(receptors,)-470.4(as)-464.2(well)-465.8(as)-470.1(a)]TJ T* [(program)-489.6(of)-480.1(gene)-490.4(expression)-489.5(associated)-489.6(with)-485.8(senescence)-492(\()]TJ 0 0 0 0.7 k 24.1392 0 TD (41)Tj 0 0 0 1 k 0.9608 0 TD (\).)Tj -25.1 -1.2114 TD [(Thus,)-229.6(the)-231(gradual)-230.6(evolution)-233.4(of)-229.5(ligand)-231.4(af)]TJ /F7 1 Tf 15.5398 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-229.3(may)-232.5(be)-223.8(the)-231(result)-230.8(of)]TJ -16.0709 -1.2114 TD 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[(receptor-ligand)-321.1(dwell)-315.8(times,)-313.5(with)-312.7(only)-315.8(very)-315.1(long)-315.8(interactions)-315.8(or)]TJ 0 -1.2055 TD [(sequential,)-444.7(spatially)-439.9(co-localized)-439(interactions)-441.1(leading)-442(to)-433.3(T)-442.3(cell)]TJ 0 -1.2114 TD [(activation)-234.5(\()]TJ 0 0 0 0.7 k 4.4936 0 TD (50)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-232.7(As)-238(such)-233.8(events)-236.2(were)-233.6(rare,)-241.9(heterogeneity)-235.6(naturally)]TJ -5.4544 -1.2114 TD [(arose.)-362.6(Moreover,)-366.7(the)-362.3(distribution)-361.6(of)-360.8(ef)56.5(fective)-359.2(dwell)-363.6(times)-364.4(a)-362.7(cell)]TJ T* [(might)-316.5(experience)-320.3(was)-318.3(found)-319.4(to)-314(be)-313.3(tuned)-320.8(by)-313.1(parameters)-324.2(such)-317.4(as)]TJ T* [(the)-505.5(af)]TJ /F7 1 Tf 2.4288 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-509.8(of)-504(the)-511.5(TCR-li)-9.1(gan)-8.2(d)-500.5(inte)-8.7(ract)-8.7(ion)-507.2(\()]TJ 0 0 0 0.7 k 15.5577 0 TD (50)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-507.2(Acc)-8.7(ordi)-9(ngly,)]TJ -19.4784 -1.2114 TD [(work)-339.2(in)-338.8(both)-339.2(nave)-340.7(CD8)]TJ 7.1249 0 0 6.3326 140.3716 180.3968 Tm (+)Tj 9.5 0 0 9.5 147.6283 176.1448 Tm [(T)-340.8(cells)-339(and)-340(ef)62.5(fector)-342.7(CTLs)-341.4(has)-338.9(shown)]TJ -10.7657 -1.2114 TD [(that)-385.4(TCR-ligand)-380.5(interaction)-387.4(strength)-386.2(modulates)-384.6(the)-386.1(mean)-384(and)]TJ 0 -1.2055 TD [(var)-12.1(ia)-7.2(n)-8(c)0(e)-510.7(o)0(f)-510(t)0(i)-10.9(m)0(e)-508.6(t)0(o)-510.9(r)0(e)-7.7(s)0(p)-11.2(o)0(n)-9.3(s)0(e)-7.7(.)-510.1(Stu)-11(di)-7.7(es)-515(usin)-15.8(g)-508.8(s)0(i)-8.6(ngl)-10.2(e-c)-13.5(el)-8.3(l)-507.9(R)0(N)-7.6(A)]TJ 0 -1.2114 TD [(se)-7.7(q)-9.2(uen)-14.9(cin)-12.3(g)-508.8(and)-519.1(ma)-10.2(ss)-513.3(and)]TJ /F7 1 Tf 11.5295 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(o)-7.2(w)-510.6(cy)-9.2(tom)-9.2(e)-7.7(t)0(r)-8.3(y)-508.8(to)-510.9(e)-7.7(x)0(a)-8.1(m)0(i)-8.2(n)-8(e)-509(na)-15.2(ve)]TJ -12.0606 -1.2114 TD (CD8)Tj 7.1249 0 0 6.3326 63.0425 134.3622 Tm (+)Tj 9.5 0 0 9.5 70.5827 130.1669 Tm [(T)-364.7(cell)-362.8(activation)-365.8(showed)-363.7(that)-367.5(strong)-365.3(stimuli)-365(drove)-361.8(more)]TJ -2.6556 -1.2114 TD [(uniform,)-235.7(rapid)-232.4(initiation)-233.9(of)-229.5(activation)-234.5(events)-230.2(including)-238.3(signaling,)]TJ T* 0.0105 Tc [(transcr)10.5(i)-10(ption,)-511.5(cell)-509.3(divis)10.5(i)-10(on,)-505.5(a)]TJ 12.359 0 TD 0.0112 Tc [(nd)-507.2(trans)11.2(c)-8.5(ription)-510(f)3.8(actor)-508(n)3.2(uclear)]TJ -12.359 -1.2114 TD 0 Tc [(localization,)-339.2(while)-342.6(weak)-338.2(stimuli)-341.2(induced)-339.9(responses)-340.3(with)-336.6(greater)]TJ 0 -1.2055 TD [(temporal)-409.3(variance)-412.7(and)-405.7(occurred,)-413.5(on)-409.1(average,)-412.4(later)-409.2(\()]TJ 0 0 0 0.7 k 21.3881 0 TD (51)Tj /F8 1 Tf 0 0 0 1 k 0.9608 0 TD ()Tj /F6 1 Tf 0 0 0 0.7 k 0.5073 0 TD (55)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-405.8(In)]TJ -23.8169 -1.2114 TD [(ef)62.5(fector)-474(CTLs,)-475.5(live)-477.9(imaging)-474(demonstrated)-479.7(the)-469.7(same)-477.4(strength-)]TJ 27.4512 67.1361 TD [(dependent)-277.8(ef)62.5(fects)-275.8(with)-276.9(respect)-275.4(to)-272.2(polarization)-279.6(of)-271.2(the)-272.8(centrosome)]TJ 0 -1.2114 TD [(and)-346(cytolytic)-343.9(granules)-350(toward)-345(the)-344.4(immunological)-345.6(synapse)-349.3(\()]TJ 0 0 0 0.7 k 24.1392 0 TD (56)Tj 0 0 0 1 k 0.9608 0 TD (\).)Tj -25.1 -1.2114 TD [(All)-227.3(of)-229.5(these)-232.7(studies)-231.9(used)-232.9(transgenic)-233.5(T)-227.4(cells)-231.6(with)-229.2(ligands)-231.4(of)-229.5(known)]TJ T* [(binding)-423(af)]TJ /F7 1 Tf 4.1714 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nities.)-419.9(Extrapolating)-423.5(to)-421.4(physiological)-423.5(contexts)-420.8(with)]TJ -4.7025 -1.2114 TD [(p)-11.1(o)-7.3(l)-6.6(y)-7.5(c)-7.7(l)-12.6(o)-7.3(n)-8(al)-524.4(T)-513.9(c)-7.7(e)-13.7(l)-6.6(l)-513.9(p)-11.1(o)-7.3(p)-11.1(ul)-11.8(a)-10.6(t)-8.3(i)-8.5(o)-7.3(n)-8(s)-12(,)-516(t)-8.3(he)-13.8(i)-8.5(r)-519.2(re)-19.7(su)-17.1(l)-6.6(t)-8.3(s)-513.2(s)-12(u)-11.1(g)-7.5(g)-7.5(e)-7.7(st)-527.5(t)-8.3(h)0(a)-16.7(t)-515.6(t)-8.3(h)0(e)]TJ T* [(response)-459.6(times)-459.8(of)-450.3(individual)-461.7(cells)-458.3(are)-453.9(sampled)-464.5(from)-455.9(dif)62.5(ferent)]TJ 0 -1.2055 TD [(dist)-10.1(ribu)-9(tions)-8.3(.)-504.1(Cells)-510.8(tha)-7.1(t)-503.6(activa)-11.4(te)-505.4(at)-502.3(di)-7.7(f)64.2(f)0(e)-9.1(rent)-507.5(times)-513.6(may)-507(then)]TJ 0 -1.2114 TD 0.019 Tc [(experie)5.3(n)-1(ce)-513.9(dif)65.3(f)-0.3(eren)5(ces)-512.1(in)-514.2(repeat)-520.4(TC)6.6(R)-518.8(e)-0.6(n)5(g)-0.4(agemen)5(t,)-514.9(cel)6.4(l-c)5.3(e)-0.6(ll)]TJ T* 0.0582 Tc [(in)-3.5(te)-3.2(rac)-3.2(t)2.1(i)-4.1(o)3.2(n)-3.5(s)-556.5(or)-562.5(mic)-3.2(r)-1.5(oe)-3.2(nviron)-3.5(men)-3.5(t)-558.8(c)-3.2(o)3.2(mposit)-3.8(ion)-558.5(durin)-3.5(g)]TJ T* 0 Tc [(activation)-455.3(and/or)-461(expansion.)-455.4(As)-458.8(described)-455.1(below,)-458.6(all)-453.5(of)-456.2(these)]TJ T* 0.0321 Tc [(features)-534.9(have)-530.6(the)-530.6(c)0.5(apacity)-530.4(t)-0.1(o)-536.1(p)3.1(ropagate)-530.6(he)-5.4(teroge)-5.4(neity)-530.4(t)-0.1(o)]TJ T* 0 Tc [(subsequent)-303.2(stages)-302.7(of)-301.1(the)-302.6(T)-299(cell)-303.1(response.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 543.6849 Tm [(HETEROGENEITY)-307.6(OF)-300.6(GENE)-301.4(EXPRESSION)]TJ /F6 1 Tf 9.5 0 0 9.5 306.1417 523.6723 Tm [(The)-360.6(stimulation)-363.4(strength)-362.3(that)-355.6(a)-362.7(nave)-358.6(T)-364.7(cell)-356.9(senses)-363.7(through)-362.7(its)]TJ T* 0.028 Tc [(TCR,)-529.8(as)-527(well)-527.6(as)-533(costimulator)]TJ 13.1169 0 TD 0.031 Tc [(y)-525.5(a)2.5(nd)-523.2(cy)5.6(t)4.8(o)-0.1(ki)4.5(ne)-525.7(r)7.1(e)-0.6(c)5.4(e)-0.6(pt)4.8(or)7.1(s)-530(a)2.5(s)]TJ -13.1169 -1.2114 TD 0.0172 Tc [(discu)-5.9(ssed)-519.1(f)-2.1(urther)-519.9(below,)-522.7(may)-515.4(a)-5.3(l)4.6(t)-3.1(er)-514(gene)-521.6(expression)-521.9(in)-516(the)]TJ T* 0 Tc [(activating)-366.1(cell)-356.9(or)-365.3(its)-357.1(progeny.)-368.2(Studies)-366.6(in)-356.7(both)-363.1(CD4)]TJ 7.1249 0 0 6.3326 502.9227 493.3983 Tm (+)Tj 9.5 0 0 9.5 510.4629 489.1463 Tm [(and)-363.9(CD8)]TJ 7.1249 0 0 6.3326 545.8392 493.3983 Tm (+)Tj 9.5 0 0 9.5 306.1417 477.6377 Tm [(T)-490(cells)-488.2(found)-492.5(that,)-489.7(among)-486.5(cells)-488.2(that)-492.8(surpassed)-493.4(an)-490(activation)]TJ 0 -1.2055 TD [(thresh)-10.4(old,)-505.2(stimula)-9(tion)-503.6(str)-8.4(ength)-503.1(corr)-9.1(elated)-505.6(wit)-8.2(h)-501.4(express)-12.2(ion)-501.2(of)]TJ 0 -1.2114 TD (speci)Tj /F7 1 Tf 1.9813 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(c)-425.4(transcripts)-438.7(and)-429.6(proteins,)-435.8(often)-426.6(many)-431.5(hours/days)-435.9(after)]TJ -2.5124 -1.2114 TD [(stimulation)-315.7(\()]TJ 0 0 0 0.7 k 5.2038 0 TD (52)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.5311 0 TD (55)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.5311 0 TD (57)Tj /F8 1 Tf 0 0 0 1 k 0.9608 0 TD ()Tj /F6 1 Tf 0 0 0 0.7 k 0.5073 0 TD (64)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-310.3(Such)-314.8(ef)62.5(fects)-311.6(may)-316(be)-307.4(modulated)-318.1(not)]TJ -10.6105 -1.2114 TD [(only)-393.4(by)-396.7(transcriptional)-396.1(processes,)-402.5(but)-390.7(also)-394.5(post-transcriptional)]TJ T* [(and)-352(translational)-356.1(mechanisms)-358.2(\()]TJ 0 0 0 0.7 k 12.8484 0 TD (9)Tj 0 0 0 1 k 0.4774 0 TD (,)Tj 0 0 0 0.7 k 0.5729 0 TD (65)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-358(For)-352.6(example,)-353.9(weak)-356.1(TCR)]TJ -14.8535 -1.2114 TD [(stimulation)-250(was)-240.7(found)-247.8(to)-242.3(be)-247.7(a)-243.3(poor)-246.5(driver)-243.8(of)-247.4(autocrine/paracrine)]TJ T* [(IL2)-280.2(production,)-292.2(which)-282.4(resulted)-285.4(in)-285.1(defective)-282.5(ribosome)-288.3(biogenesis)]TJ 0 -1.2055 TD [(and)-447.5(translation)-446.3(compared)-449(with)-444(strongly)-445.1(stimulated)-453.9(cells)-446.4(\()]TJ 0 0 0 0.7 k 24.1392 0 TD (64)Tj 0 0 0 1 k 0.9608 0 TD (\).)Tj -25.1 -1.2114 TD [(How)-235.2(TCR-ligand)-237.2(af)]TJ /F7 1 Tf 7.7818 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(nity)-235.3(might)-232.9(initiate)-241.6(control)-236.2(over)-237.3(biosynthetic)]TJ -8.3129 -1.2114 TD [(processes)-310.2(is)-307(not)-310(clear,)-304(but)-307.2(one)-309.4(possibility)-312.4(is)-307(that)-301.9(it)-309.3(relates)-309.5(to)-308(the)]TJ T* [(duration)-202.3(of)-199.6(signals)-208.4(the)-201.1(T)-197.6(cell)-201.7(receives.)-204.9(The)-205.4(duration)-202.3(of)-199.6(T)-203.6(cell-APC)]TJ T* [(interactions)-226.3(has)-225.6(been)-227.6(shown)-227.6(both)]TJ /F11 1 Tf 13.4869 0 TD [(in)-219.5(vitro)]TJ /F6 1 Tf 3.0912 0 TD (and)Tj /F11 1 Tf 1.7247 0 TD [(in)-225.4(vivo)]TJ /F6 1 Tf 2.8645 0 TD [(to)-224.4(correlate)]TJ -21.1673 -1.2114 TD [(with)-324.7(stimulation)-333.6(strength)-326.5([exempli)]TJ /F7 1 Tf 14.0717 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(ed)-329.1(by)-325.1(\()]TJ 0 0 0 0.7 k 2.8943 0 TD (29)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.549 0 TD (44)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.5431 0 TD (66)Tj /F8 1 Tf 0 0 0 1 k 0.9608 0 TD ()Tj /F6 1 Tf 0 0 0 0.7 k 0.5132 0 TD (68)Tj 0 0 0 1 k 0.9548 0 TD [(\)],)-331.3(and)]TJ -22.9277 -1.2055 TD [(re)-7.7(c)-7.7(e)0(n)-9.8(t)-509.6(st)-8.4(ud)-10.3(ie)-10.3(s)-507.3(s)0(u)-11.2(g)-7.5(ge)-9.2(st)-509.6(t)-8.3(h)0(a)-10.7(t)-503.6(si)-14.5(gn)-9.5(al)-512.5(du)-10.3(ra)-10.6(ti)-10.9(on)-510.6(c)-7.7(a)0(n)-513.9(i)0(m)-8.1(p)0(a)-9.8(c)-7.7(t)-503.6(g)-7.5(e)-7.7(n)0(e)]TJ 0 -1.2114 TD [(expression.)-331.2(For)-322.8(example,)-330.1(use)-323.2(of)-325(a)-326.9(pharmacological)-328.6(intervention)]TJ T* 0.0369 Tc [(to)-537.3(interru)-4.1(pt)-538.3(TCR)-536.7(s)1.1(ignals)-536(after)-536(d)1.9(if)59.4(ferent)-538.4(periods)-536(o)-0.2(f)-537.4(t)-1.3(ime)]TJ T* 0 Tc [(demonstrated)-330.5(dif)62.5(ferent)-325.6(signal)-327.7(durations)-327.6(required)-330(for)-325(expression)]TJ T* [(of)-408.5(early)-408.4(response)-411.9(transcription)-414.8(factors)]TJ /F11 1 Tf 16.0948 0 TD (Nr4a1)Tj /F6 1 Tf 2.9003 0 TD (and)Tj /F11 1 Tf 1.9037 0 TD (Nr4a3)Tj /F6 1 Tf 2.9003 0 TD (\()Tj 0 0 0 0.7 k 0.3402 0 TD (69)Tj 0 0 0 1 k 0.9608 0 TD (\).)Tj -25.1 -1.2114 TD [(Likewise,)-385.3(experiments)-384.5(using)-381.3(an)-376.7(optogenetic)-381.9(construct)-386.7(to)]TJ /F7 1 Tf 23.4648 0 TD ()Tj /F6 1 Tf 0.5311 0 TD (nely)Tj -23.9959 -1.2055 TD [(control)-397.3(patterns)-400.3(of)-396.6(receptor)-402(signaling)-399.5(in)-398.5(the)-398.1(Jurkat)-400.7(T)-394.5(cell)-398.6(line)]TJ 0 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[(ce)-16.2(l)11.3(l)-16.2(s)-255.6(\()]TJ 0 0 0 0.7 k 2.22 0 TD -0.0135 Tc (96)Tj 0 0 0 1 k 0.931 0 TD 0 Tc [(\))14.8(.)-253.4(In)26.6(t)15.6(e)16.2(r)11.9(e)16.2(s)11.9(t)15.6(i)15.3(n)0(g)26.3(l)17.3(y,)-243(TC)28.7(R)-257.3(s)17.9(t)15.6(i)0(m)27.7(u)12.8(l)17.3(a)13.3(t)15.6(i)0(o)26(n)-252.7(s)11.9(t)15.6(r)11.9(e)16.2(n)15.8(g)0(t)26(h)-250.8(w)14.6(a)13.3(s)-256.6(f)16.5(ou)29.4(nd)-240(to)-242.3(b)16.6(e)]TJ -3.1509 -1.2114 TD [(positi)9.9(vely)-476.8(correlate)9.7(d)-482.6(with)-473.8(CXCR3)-476.9(expressi)9.1(on)-480.8(\()]TJ 0 0 0 0.7 k 19.5142 0 TD (67)Tj 0 0 0 1 k 0.9548 0 TD [(\),)-477.4(as)-482(well)-477.8(as)]TJ -20.4691 -1.2055 TD -0.0149 Tc [(reten)-14.9(t)10.5(ion)-327.3(o)-14.9(f)-310(T)-331.9(cel)-14.9(l)13.7(s)-325.2(in)-327.3(the)-327(s)3(pl)-14.9(e)12.6(e)1.3(n)-327.3(\()]TJ 0 0 0 0.7 k 13.5048 0 TD -0.0135 Tc (39)Tj 0 0 0 1 k 0.931 0 TD -0.0145 Tc [(\))-327.9(a)4.8(n)-14.5(d)-314.1(IFR)-325.5(l)-14.5(o)13.4(c)1.7(al)-14.5(i)12.1(z)1.7(atio)-14.5(n)-316.2(i)0.8(n)-320.9(t)-14.5(h)12.9(e)]TJ -14.4358 -1.2114 TD -0.0173 Tc [(ly)-17.3(m)11.4(p)-4.6(h)-321.8(n)-1.5(o)-17.3(d)12.1(e)-323.4(\()]TJ 0 0 0 0.7 k 5.3828 0 TD -0.0135 Tc (67)Tj 0 0 0 1 k 0.931 0 TD 0 Tc [(\))14.8(.)-301.2(It)-290(i)15.3(s)-304.4(t)15.6(h)11.8(e)16.2(r)11.9(e)16.2(f)0(o)27.1(r)17.9(e)-306.1(t)15.6(em)28.5(p)12.8(t)15.6(i)15.3(n)0(g)-290(t)15.6(o)-305.6(h)17.8(yp)23.2(o)16.6(t)15.6(h)11.8(e)16.2(s)11.9(i)15.3(z)16.2(e)-306.1(a)-303(c)16.2(a)13.3(u)12.7(s)17.9(a)13.3(l)]TJ -6.3138 -1.2114 TD [(s)11.9(e)16.2(q)14.7(u)12.7(e)16.2(n)15.8(ce)-331.7(w)14.6(h)17.8(er)28.1(eb)26.8(y)-341.7(s)17.9(t)15.6(r)11.9(o)16.6(n)0(g)-325.8(s)11.9(t)15.6(i)15.3(m)12.3(u)12.8(l)17.3(a)13.3(t)15.6(i)0(o)26(n)-342.2(u)18.7(p)12.8(r)11.9(e)16.2(gu)29.1(la)24.6(t)15.6(e)16.2(s)-340.2(C)0(X)29.9(C)0(R)28.7(3)13.5(,)-343(w)14.6(h)11.8(i)15.3(c)16.2(h)]TJ T* [(d)12.7(i)15.3(r)11.9(e)16.2(c)16.2(t)15.6(s)-286.5(c)16.2(el)27.5(l)17.3(s)-286.5(t)15.6(o)-281.8(t)15.6(h)11.8(e)-282.2(l)17.3(ym)28.7(p)12.7(h)-280.6(no)26.5(d)12.8(e)-282.2(I)16.7(F)12.8(R)-281.1(a)13.3(n)15.8(d)-285.6(p)12.8(r)17.9(ov)27(i)15.3(d)12.8(e)16.2(s)-286.5(a)13.3(n)-282.5(e)16.2(n)15.8(vi)25.7(r)11.9(o)16.6(n)15.8(m)12.3(e)16.2(n)15.8(t)]TJ T* -0.015 Tc [(that)-238.2(driv)-15(e)11.6(s)-241.8(ef)61.2(f)-15(e)11.7(cto)-15(r)-225.2(dif)61.2(f)-15(e)11.7(r)-3.1(enti)-15(a)13.6(t)-15(i)9.9(o)1.6(n)-243.8(\()]TJ /F10 1 Tf 0 0 0 rg 13.3437 0 TD -0.014 Tc [(Figure)-237.5(2)]TJ /F6 1 Tf 0 0 0 1 k 3.3419 0 TD [(\).)-243.7(F)4.6(u)-1.3(ture)-236.6(studies)-240.9(w)0.5(il)3.2(l)-241.5(b)2.5(e)]TJ 10.7656 66.5811 TD 0.029 Tc [(requ)5.9(ired)-513.2(to)-515.3(test)-510.4(this.)-510.9(T)-1.5(ogether,)-510.9(th)5(is)-508.1(work)-508.4(highl)4.5(i)-3.4(ghts)-514.1(how)]TJ 0 -1.2114 TD -0.0142 Tc [(h)3.6(e)-14.2(t)11.5(e)2(rog)-14.2(e)12.4(ne)-14.2(i)11.3(t)1.4(y)-308.1(o)-14.2(f)-297.4(T)-313.3(c)-14.2(e)12.2(l)3.1(l)-313.2(resp)4.5(o)-14.2(n)12.3(ses)-312.6(c)2(an)-314.6(p)4.5(r)-2.3(opagate)-314.3(f)2.3(rom)-312.2(v)2.2(ariatio)-14.2(n)-298(in)]TJ T* -0.0152 Tc [(expressi)-15.2(o)10.8(n)-226.1(of)-225.5(a)-228.7(s)-3.3(ingl)-15.2(e)-214.5(c)1(hemokine)-225.8(rec)-15.2(e)11.2(ptor)-230.1(or)-224.1(subtl)-15.2(e)-214.5(cel)-15.2(l)-213.4(p)-2.4(osition)-15.2(i)10(ng)]TJ T* 0 Tc [(a)13.3(l)17.3(l)-257.2(t)15.5(h)11.8(e)-252.4(w)14.6(a)13.3(y)-258.1(t)15.5(o)-251.9(d)12.7(i)15.3(f)76.2(fe)26.7(r)11.9(e)16.2(n)15.8(t)15.6(ia)28.6(t)15.5(i)0(o)26(n)-258.7(f)16.5(a)13.3(t)15.6(e)16.2(.)]TJ 1.2651 -1.2114 TD [(Cellular)-276.5(interactions)-280(are)-280.9(governed)-277.6(by)-277.3(localization)-282.7(and)-274.4(form)-282.8(a)]TJ -1.2651 -1.2114 TD 0.0669 Tc [(crit)4.9(ical)-536.5(part)-538.2(of)-531.3(the)-537.6(m)1.7(icroenv)5.7(i)-1.3(ronment)-532.2(t)-1.1(hat)-532.2(i)-1.3(n)]TJ /F7 1 Tf 22.0565 0 TD 0 Tc ()Tj /F6 1 Tf 0.5968 0 TD 0.067 Tc (uences)Tj -22.6532 -1.2055 TD 0.0618 Tc [(dif)61.8(f)-0.7(erenti)-6.4(ati)-6.4(o)0.8(n)-531.1(f)-5.3(ate)-536.7(d)-3(ecision)-5.9(s.)-537.8(Early)-530.5(i)-6.4(ntravi)-6.4(tal)-535.6(i)-0.5(maging)]TJ 0 -1.2114 TD 0.0094 Tc [(experiments)-480(i)0.9(mmu)9.4(n)-9.7(i)0.9(zin)-4.6(g)-475.5(with)-480.1(antig)-4(e)1.7(n-load)9.4(e)-9.4(d)-479.1(d)9.4(e)-9.4(ndr)9.4(i)-11.1(tic)-475.7(c)-4.3(ells)]TJ T* 0 Tc [(\(DCs\))-375.8(demonstrated)-378.2(that)-379.4(a)-374.6(single)-378.6(nave)-376.5(TCR)-371.8(transgenic)-382.7(T)-376.6(cell)]TJ T* [(makes)-227.1(multiple)-232.7(sequential)-227(APC)-231.4(contacts)-231(and)-226.7(that)-224.3(the)-231(duration)-226.1(of)]TJ T* [(these)-208.9(interactions)-220.3(varies)-213.4(according)-211.7(to)-212.5(the)-207.1(activation)-216.6(stage)-213.1(of)-205.6(the)-213.1(T)]TJ T* [(cell)-231.5(\()]TJ 0 0 0 0.7 k 1.9096 0 TD (98)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-232.7(As)-232.1(recently)-232.6(reviewed)-238.6(\()]TJ 0 0 0 0.7 k 9.5781 0 TD (94)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.4476 0 TD (99)Tj 0 0 0 1 k 0.9608 0 TD [(\),)-232.7(a)-225.4(large)-235.3(body)-230(of)-235.4(work)-231.8(over)]TJ -14.8117 -1.2055 TD [(the)-302.6(past)-304.6(two)-305.3(decades)-306.6(has)-309.1(mapped)-307.9(the)-302.6(architecture)-310.6(of)-301.1(the)-308.6(lymph)]TJ 0 -1.2114 TD [(node)-177.3(and)-178.9(locations)-177.7(of)-175.8(innate)-176.5(and)-178.9(adaptive)-182.9(immune)-177.8(cells)-177.9(during)-177.6(an)]TJ T* [(immune)-207.7(response.)-211.8(The)-211.4(majority)-209.5(of)-205.6(antigen)-207.9(presentation)-211(for)-211.6(nave)]TJ T* [(T)-442.3(cell)-440.4(activation)-449.4(is)-444.2(performed)-445.8(by)-444.4(conventional)-441.7(dendritic)-447.1(cells)]TJ T* [(\(cDCs\).)-272.9(Type)-277.6(1)-267(cDCs)-275.8(reside)-273.8(primarily)-279.3(in)-267.2(the)-272.8(paracortex,)-278.4(express)]TJ T* [(XCR1)-207.9(and)-202.8(are)-209.3(specialized)-212.7(in)-207.5(antigen)-207.9(cross-presentation)-212.2(to)-206.5(engage)]TJ 0 -1.2055 TD (CD8)Tj 7.1249 0 0 6.3326 323.8298 507.6849 Tm (+)Tj 9.5 0 0 9.5 330.8598 503.4897 Tm [(T)-305(cells)-309.1(\()]TJ 0 0 0 0.7 k 3.2643 0 TD (99)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-310.3(Intravital)-308.4(imaging)-306.9(studies)-309.5(demonstrated)-312.6(that)]TJ -6.827 -1.2114 TD [(cDC1s)-190.7(serve)-196(as)-195.6(a)-189.6(communication)-199.7(link)-190.6(between)-193.3(CD4)]TJ 7.1249 0 0 6.3326 498.5007 496.1762 Tm (+)Tj 9.5 0 0 9.5 504.3967 491.981 Tm [(and)-190.9(CD8)]TJ 7.1249 0 0 6.3326 538.1857 496.1762 Tm (+)Tj 9.5 0 0 9.5 544.0818 491.981 Tm (T)Tj -25.0463 -1.2114 TD [(cells)-297.2(on)-295.8(the)-296.6(second)-298.5(day)-291.8(after)-302.6(infection,)-295.1(simultaneously)-301.9(engaging)]TJ T* [(cells)-297.2(from)-300.7(both)-303.4(lineages)-301.4(and)-298.3(facilitating)-303.5(CD4)]TJ 7.1249 0 0 6.3326 477.3542 473.1589 Tm (+)Tj 9.5 0 0 9.5 484.2708 468.9637 Tm [(T)-299.1(cell)-297.2(help)-300.1(to)-302(the)]TJ -18.7504 -1.2114 TD (CD8)Tj 7.1249 0 0 6.3326 323.8298 461.707 Tm (+)Tj 9.5 0 0 9.5 331.0865 457.455 Tm [(T)-334.9(cell)-333(response)-340.3(\()]TJ 0 0 0 0.7 k 6.7852 0 TD (100)Tj 0 0 0 1 k 1.4382 0 TD (,)Tj 0 0 0 0.7 k 0.549 0 TD (101)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-334.1(Inducible)-337.8(depletion)-339(of)-336.9(cDC1s)]TJ -12.8364 -1.2114 TD [(disrupted)-194.4(clusters)-196.7(of)-193.7(antigen-speci)]TJ /F7 1 Tf 13.4451 0 TD ()Tj /F6 1 Tf 0.5311 0 TD [(c)-192.7(CD4)]TJ 7.1249 0 0 6.3326 462.444 450.1983 Tm (+)Tj 9.5 0 0 9.5 468.34 445.9464 Tm [(and)-190.8(CD8)]TJ 7.1249 0 0 6.3326 502.0724 450.1983 Tm (+)Tj 9.5 0 0 9.5 507.9684 445.9464 Tm [(T)-191.6(cells,)-198.6(and)]TJ -21.2449 -1.2114 TD [(skewed)-227.2(CD8)]TJ 7.1249 0 0 6.3326 353.4236 438.6896 Tm (+)Tj 9.5 0 0 9.5 359.6598 434.4377 Tm [(T)-227.4(cell)-225.6(dif)56.5(ferentiation)-227.7(from)-229.1(memory)-230.5(toward)-231.6(ef)62.5(fector)]TJ -5.6335 -1.2055 TD 0.0306 Tc [(pa)-3.8(thways)-500.5(\()]TJ 0 0 0 0.7 k 4.8517 0 TD 0.0342 Tc [(10)6(0)]TJ 0 0 0 1 k 1.5277 0 TD 0.0325 Tc [(\).)-501.4(Type)-500.4(2)-497(c)0.9(DCs)-498.7(a)4(re)-494.4(often)-500.7(c)0.9(haract)6.3(erized)-497.8(by)]TJ -6.3794 -1.2114 TD 0 Tc [(expression)-364.2(of)-360.8(CD11b)-713.7(\(ITGAM\))-365.8(and)-357.9(tend)-363.4(to)-355.7(reside)-363.4(in)-356.7(the)-362.3(IFR)]TJ T* [(and)-316.2(T)-317(cell-B)-321(cell)-321(border)-313.9(regions)-325.5(of)-313(the)-320.5(lymph)-317.4(node)-320.6(\()]TJ 0 0 0 0.7 k 21.3941 0 TD (99)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-316.2(While)]TJ -22.3548 -1.2114 TD [(these)-441.6(DCs)-441.1(have)-437.7(been)-442.5(best)-441(described)-443.1(for)-444.3(their)-436.5(contribution)-448.5(to)]TJ T* (CD4)Tj 7.1249 0 0 6.3326 323.8298 381.2031 Tm (+)Tj 9.5 0 0 9.5 332.2204 376.9511 Tm [(T)-448.2(cell)-452.3(responses,)-450.5(it)-452.5(is)-450.2(speculated)-452(that)-451(they)-453.3(and)-447.5(nearby)]TJ -2.7451 -1.2114 TD 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[(Likewise,)-302.5(organism)-300.9(age)-298.9(at)-300.5(thymic)-304.9(egress)-300.5(\(particularly)-310.4(adult)-300.2(versus)-300.6(fetus\))-299.9(and)-306.5(the)-295.9(strength)-309.7(of)-299.5(self-pMHC)-299.7(interaction)]TJ -19.3731 -1.3526 TD [(during)-297.4(positive)-307.2(selection)-296.5(af)55.4(fect)-301.8(gene)-294.4(expression)-307.2(and)-298.4(response)-307.1(characteristics)-305.7(of)-299.5(peripheral)-304(nave)-300.5(T)-298.4(cells;)-306.8(cTEC,)-303.8(cortical)-297.9(thymic)-304.9(epithelial)-304.3(cell;)]TJ 59.561 0 TD [(DP,)-298.9(double-positive.)]TJ /F1 1 Tf 8.9414 0 TD (\(D\))Tj /F4 1 Tf -68.5025 -1.3607 TD [(Cytokines)-300.1(and)-298.4(other)-306.7(environmental)-300.2(components)-303.3(tune)-307.6(nave)-300.5(cell)-302.6(reactivity.)]TJ /F1 1 Tf 31.376 0 TD (\(E\))Tj /F4 1 Tf 1.5307 0 TD [(Cartoon)-296.9(histograms)-308.5(depict)-300(the)-304.1(probability)-303.3(of)-299.5(a)-299.9(cell)-302.6(exhibiting)-303.7(a)-299.9(certain)-301.5(phenotype)-308.3(\(e.g.)]TJ -32.9068 -1.3526 TD [(expression)-299.1(of)-299.5(CD8)-301.3(or)-302.3(a)-299.9(particular)-301.6(metabolic)-309.3(state\).)-301.5(Stochastic)-302.6(variation)-304.9(as)-298.8(in)]TJ /F1 1 Tf 32.6314 0 TD (\(A\))Tj /F4 1 Tf 1.555 0 TD [(creates)-304(a)-299.9(distribution)-302.9(\(black\))-306.4(which)-298.2(might)-307.9(then)-299.5(be)-303(tuned)-302.6(in)-296.3(variance)-304.9(\(green\))-306.2(and/or)]TJ -34.1864 -1.3607 TD [(mean)-299.8(\(magenta\))-307.3(by)-298.3(additional)-304.6(factors)-303.3(such)-297.8(as)]TJ /F1 1 Tf 19.7295 0 TD (\(B)Tj /F15 1 Tf 0.9962 0 TD ()Tj /F1 1 Tf 0.494 0 TD (D\))Tj /F4 1 Tf 1.0367 0 TD [(.)-296.9(All)-300.7(cells)-301.4(represent)-306.1(nave)-300.5(T)-298.4(cells)-301.4(unless)-297.8(otherwise)-305(speci)]TJ /F5 1 Tf 23.4875 0 TD ()Tj /F4 1 Tf 0.4374 0 TD [(ed.)-300.3(Created)-307.5(with)-303(Biorender.com.)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Richard)Tj 60.7921 0 TD (CD8)Tj 5.2498 0 0 4.6661 484.3841 747.3824 Tm (+)Tj 6.9999 0 0 6.9999 489.5999 744.2644 Tm [(T)-298.4(Cell)-301.8(Heterogeneity)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 54.6692 0 TD [(July)-302.1(2022)-505.2(|)-494.7(Volume)-307.7(13)-499.6(|)-494.7(Article)-305.6(949423)]TJ -18.9034 0 TD (9)Tj ET endstream endobj 255 0 obj<>stream Adobed         s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz ?N*UثWb]v*UثWb]Qջ;xORWTZbJ1'[n/Vh"=H:ªHbG5U]v*Uت_{-PVK{yeAZnHe ywQl6z6 v㶝PAF'7ݑr\8+e?>oN,zƱ7~"haQ@Zr#Y-;W\3nA31{Zzio5H14z̜ZLbX~gy[[դًֈ1UÓEJeshrO@1V'k~_7 oyY˳F' q2sHX`r>uJN)wOl.&? 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-1.2114 TD 0 Tc ()Tj /F6 1 Tf 0.549 0 TD 0.0197 Tc [(n)-6.2(d)-3.4(ings)-219(d)-3.4(i)-0.8(s)-4.2(c)0.1(u)-3.4(s)1.8(s)-4.2(e)0.1(d)-218.2(h)-4.3(er)-4.2(e)-214.8(s)-4.2(u)-3.4(gge)-5.9(st)-221.4(that)-215.4(wh)-4.3(ile)-220.7(g)0.3(e)-5.9(n)-0.3(e)-214.8(e)-5.9(xp)-3.4(re)-5.9(ss)-4.2(ion)-221.1(a)3.2(n)-6.2(d)]TJ -0.549 -1.2114 TD 0.0369 Tc [(cel)6.4(lular)-512.2(i)-1.5(n)5(t)-1.3(eract)4.7(i)-1.5(on)5(s)-518.1(b)-0.2(e)-513.9(g)5.6(overn)5(e)-0.6(d)-517.3(b)5.8(y)-513.6(s)1.1(tochasti)4.5(c)-513.9(p)1.9(rocesses)]TJ T* 0.0223 Tc [(for)4.4(m)-1.2(ing)-450.7(t)2(he)-450.9(backdr)4.4(op)-448.3(for)-449.2(t)2(hese)-450.9(events)-449.2(is)-449.2(h)4.3(e)-3.3(a)5.8(v)-3.1(il)3.8(y)-450.7(i)-4.1(m)4.8(p)-0.8(acted)]TJ T* 0.0532 Tc [(by)-527.2(th)5.3(e)-533.4(n)-2.6(atural)-532.3(his)5.4(t)-2.9(ory)-533.1(o)-1.8(f)-527.1(t)-2.9(he)-527.4(cel)4.8(l.)-534.4(T)4.8(h)-0.6(us,)-534.4(a)0.9(lthou)-5.7(g)3.9(h)-531.7(n)-2.6(ot)]TJ 0 -1.2055 TD 0.0782 Tc 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4.2709 0 TD [(\(2020\))-225.1(217\(10\):e20191711.)]TJ -19.6311 -1.2624 TD [(doi:)-301.1(10.1084/jem.20191711)]TJ -1.6781 -1.2699 TD [(16.)-502.1(Johnnidis)-462.1(JB,)-456.9(Muroyama)-455(Y,)-449.6(Ngiow)-457.7(SF,)-457(Chen)-456.3(Z,)-451.4(Manne)-460.6(S,)-447.9(Cai)-461.2(Z,)-451.4(et)-453.7(al.)]TJ 1.6781 -1.2624 TD [(In)-18(hi)-17.8(bi)-11(t)-7.9(o)-14(ry)-523.5(Si)-12.8(g)-10.7(n)0(a)-12.2(l)0(i)-19.1(n)-10.8(g)-509.6(S)0(u)-17.4(s)-14(t)-7.9(a)-9(in)-15.4(s)-512.9(a)-515.4(D)-11.8(i)0(s)-11(t)-7.9(i)-12.1(n)0(c)-18.1(t)-514.4(Ea)-13.9(rl)-13.4(y)-517.1(M)0(e)-21.8(m)0(o)-10.8(r)0(y)-523.5(C)-9.2(d)-9.1(8)0(\()-17.1(+)-10.1(\))-511.2(T)-519.9(C)-9.2(e)0(l)-14.3(l)]TJ 0 -1.2699 TD [(Precursor)-400.9(That)-406.4(Is)-391.5(Resistant)-406.3(to)-399.9(DNA)-392.4(Damage.)]TJ /F11 1 Tf 19.3136 0 TD [(Sci)-401.3(Immunol)]TJ /F6 1 Tf 5.5711 0 TD [(\(2021\))-399(6\(55\):)]TJ -24.8847 -1.2699 TD [(eabe3702.)-307.4(doi:)-301.1(10.1126/sciimmunol.abe3702)]TJ -1.6781 -1.2624 TD [(17.)-502.1(Pais)-508.7(Ferreira)-510(D,)-496.8(Silva)-508.1(JG,)-505.7(Wyss)-499.2(T,)-506(Fuertes)-507.1(Marraco)-505(SA,)-501.7(Scarpelli)-13(no)-501.1(L,)]TJ 1.6781 -1.2699 TD [(Charmoy)-429.7(M,)-423.9(et)-423.4(al.)-425.4(Central)-428(Memory)-427.7(Cd8\(+\))-428.1(T)-421.6(Cells)-430(Derive)-426(From)-427(Stem-)]TJ 0 -1.2624 TD [(Like)-435.7(Tcf7\(Hi\))-432.3(Ef)59.3(fector)-432.3(Cells)-430(in)-431.1(the)-436.7(Absence)-432(of)-426(Cytotoxic)-439.1(Dif)63(ferentiation.)]TJ /F11 1 Tf 0 -1.2699 TD (Immunity)Tj /F6 1 Tf 4.2709 0 TD [(\(2020\))-300.7(53\(5\):985)]TJ /F8 1 Tf 6.6898 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(1000.e11.)-303(doi:)-301.1(10.1016/j.immuni.2020.09.005)]TJ -13.1454 -1.2624 TD [(18.)-502.1(Buggert)-429.1(M,)-431.5(Vella)-429.4(LA,)-423.5(Nguyen)-428.3(S,)-432.7(Wu)-424.5(VH,)-426.4(Chen)-433.6(Z,)-421.1(Sekine)-433.6(T,)-430.4(et)-423.4(al.)-425.4(The)]TJ 1.6781 -1.2699 TD 0.0136 Tc [(Identity)-511.1(of)-511.8(Hum)-5.9(a)4.6(n)-518.8(T)0.2(issue-)4.8(Em)-5.9(igrant)-515.9(Cd8)-6.3(\()1.3(+\))-520.3(T)-513.8(C)4.4(ells.)]TJ /F11 1 Tf 23.4938 0 TD 0.0167 Tc (Cell)Tj /F6 1 Tf 2.0712 0 TD 0.0123 Tc [(\(20)-7.6(20\))-514(183)]TJ -25.565 -1.2699 TD 0 Tc (\(7\):1946)Tj /F8 1 Tf 3.3033 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(61.e15.)-301(doi:)-301.1(10.1016/j.cell.2020.11.019)]TJ -5.4955 -1.2624 TD [(19.)-502.1(Poon)-210.1(MML,)-217.4(Byington)-212.1(E,)-210.2(Meng)-217.2(W,)-212.4(Kubota)-212(M,)-212.3(Matsumoto)-208.2(R,)-211.2(Grifoni)-213(A,)-213.7(et)-211.8(al.)]TJ 1.6781 -1.2699 TD [(Heterogeneity)-445.8(of)-441.1(Human)-437.4(Anti-Viral)-443.9(Immunity)-444.5(Shaped)-441.6(by)-440.4(Virus,)-441.9(Tissue,)]TJ 0 -1.2624 TD 0.0993 Tc [(Age,)-589.8(and)-590.2(S)0.4(ex.)]TJ /F11 1 Tf 7.7179 0 TD 0.0941 Tc [(Ce)-9.8(ll)-604.2(Rep)]TJ /F6 1 Tf 4.8454 0 TD 0.096 Tc [(\(20)-7.1(21\))-596.6(3)-7.1(7)0.5(\(9)-7.1(\):1100)-7.1(71.)-600.7(doi:)-600.7(10.10)-7.1(16/)]TJ -12.5633 -1.2699 TD 0 Tc (j.celrep.2021.110071)Tj -1.6781 -1.2624 TD [(20.)-502.1(Stemberger)-306.7(C,)-297.7(Huster)-305.2(KM,)-302.2(Kof)]TJ /F7 1 Tf 14.1734 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(er)-301(M,)-303(Anderl)-306.1(F,)-297.6(Schiemann)-302.4(M,)-303(Wagner)-308.3(H,)]TJ -13.0244 -1.2699 TD [(et)-453.7(al.)-448.1(A)-446.9(Single)-449.2(Naive)-449.1(Cd8+)-448.9(T)-451.8(Cell)-446.3(Precursor)-453.8(Can)-452.3(Develop)-445.2(into)-453.1(Diverse)]TJ T* [(Ef)59.3(fector)-266(and)-263.3(Memory)-261.4(Subsets.)]TJ /F11 1 Tf 12.2231 0 TD (Immunity)Tj /F6 1 Tf 4.2331 0 TD [(\(2007\))-262.9(27\(6\):985)]TJ /F8 1 Tf 6.6445 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(97.)-260.2(doi:)-263.3(10.1016/)]TJ -23.6148 -1.2624 TD (j.immuni.2007.10.012)Tj -1.6781 -1.2699 TD [(21.)-502.1(Gerlach)-370.3(C,)-358.1(van)-363.1(Heijst)-361.7(JW,)-366.7(Swart)-367.4(E,)-361.4(Sie)-360.3(D,)-368.3(Armstrong)-362.7(N,)-365.8(Kerkhoven)-366.1(RM,)]TJ 1.6781 -1.2624 TD [(et)-264.7(al.)-259.1(One)-261.8(Naive)-260.1(T)-262.9(Cell,)-258.5(Multiple)-263.1(Fates)-266.5(in)-257.3(Cd8+)-259.9(T)-262.9(Cell)-257.3(Dif)63(ferentiation.)]TJ /F11 1 Tf 28.1578 0 TD [(J)-262.5(Exp)]TJ -28.1578 -1.2699 TD (Med)Tj /F6 1 Tf 2.0712 0 TD [(\(2010\))-300.7(207\(6\):1235)]TJ /F8 1 Tf 7.6423 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(46.)-298(doi:)-301.1(10.1084/jem.20091175)]TJ -11.9057 -1.2624 TD [(22.)-502.1(Khatun)-321.4(A,)-319.6(Kasmani)-323(MY,)-313(Zander)-326.5(R,)-317(Schauder)-319.2(DM,)-322.3(Snook)-314(JP,)-319.1(Shen)-319.3(J,)-321.7(et)-317.6(al.)]TJ 1.6781 -1.2699 TD [(Single-Cell)-329.8(Lineage)-327.5(Mapping)-324.8(of)-320.2(a)-326.5(Diverse)-326.5(Virus-Speci)]TJ /F7 1 Tf 21.8308 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(c)-324.8(Naive)-320.6(Cd4)-325.5(T)-323.3(Cell)]TJ -22.3675 -1.2699 TD (Repertoire.)Tj /F11 1 Tf 4.6716 0 TD [(J)-270.1(Exp)-277.4(Med)]TJ /F6 1 Tf 4.3994 0 TD [(\(2021\))-270.4(218\(3\):e20200650.)-280.6(doi:)-270.8(10.1084/jem.20200650)]TJ 7.4999 0 0 7.4999 49.8331 246.444 Tm [(23.)-502.1(Lonnberg)-193.1(T,)-188.5(Svensson)-188(V,)-188.6(James)-196.4(KR,)-187.7(Fernandez-Ruiz)-196(D,)-186.9(Sebina)-190(I,)-189.8(Montandon)]TJ 1.6781 -1.2699 TD [(R,)-324.5(et)-332.7(al.)-319.6(Single-Cell)-329.8(Rna-Seq)-333.7(and)-323.7(Computational)-327.7(Analysis)-327.8(Using)-331.5(Temporal)]TJ 0 -1.2624 TD 0.0155 Tc [(Mi)-4.2(xture)-490.7(M)1(ode)-6.9(lling)-486.5(Re)-6.9(solves)-489.8(T)2.1(h)-5.3(1)3.2(/Tfh)-489.1(Fate)-483.2(Bi)-4.2(furcati)-4.2(o)1.5(n)-486.7(i)3.4(n)-486.7(M)-6.6(alaria.)]TJ /F11 1 Tf 29.0952 0 TD 0.0107 Tc [(Sc)-7.4(i)]TJ -29.0952 -1.2699 TD 0 Tc (Immunol)Tj /F6 1 Tf 3.9383 0 TD [(\(2017\))-270.4(2\(9\):eaal2192.)-276.9(doi:)-270.8(10.1126/sciimmunol.aal2192)]TJ -5.6165 -1.2624 TD [(24.)-502.1(Buchholz)-334.9(VR,)-330.5(Flossdorf)-333.3(M,)-333.2(Hensel)-329.5(I,)-333.4(Kretschmer)-330.4(L,)-331.9(Weissbrich)-334.3(B,)-332.9(Graf)-331.7(P,)]TJ 1.6781 -1.2699 TD [(et)-340.3(al.)-334.7(Disparate)-343.6(Individual)-345.7(Fates)-334.6(Compose)-344.1(Robust)-337(Cd8+)-343.1(T)-338.5(Cell)-332.9(Immunity.)]TJ /F11 1 Tf T* (Science)Tj /F6 1 Tf 3.1068 0 TD [(\(2013\))-300.7(340\(6132\):630)]TJ /F8 1 Tf 8.6023 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(5.)-300.8(doi:)-301.1(10.1126/science.1235454)]TJ -13.8937 -1.2624 TD [(25.)-502.1(Gerlach)-377.9(C,)-380.8(Rohr)-379.7(JC,)-376.3(Perie)-378.2(L,)-377.3(van)-378.2(Rooij)-378.1(N,)-373.4(van)-378.2(Heijst)-384.4(JW,)-374.2(Velds)-383.6(A,)-372.5(et)-378.1(al.)]TJ 1.6781 -1.2699 TD [(Heterogeneous)-308.6(Dif)63(ferentiation)-306.1(Patterns)-302.6(of)-305.1(Individual)-307.9(Cd8+)-297.7(T)-300.7(Cells.)]TJ /F11 1 Tf 27.4246 0 TD (Science)Tj /F6 1 Tf -27.4246 -1.2624 TD [(\(2013\))-300.7(340\(6132\):635)]TJ /F8 1 Tf 8.6023 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(9.)-300.8(doi:)-301.1(10.1126/science.1235487)]TJ -10.7945 -1.2699 TD [(26.)-502.1(Plumlee)-477.9(CR,)-469.8(Sheridan)-476.9(BS,)-477.1(Cicek)-476.7(BB,)-468(Lefrancois)-483.5(L.)-468(Environmental)-479(Cues)]TJ 1.6781 -1.2624 TD [(Di)-16.4(cta)-16.7(t)-7.9(e)-513.8(the)-519.8(F)-9.1(a)0(t)-9.4(e)-513.8(of)-516.7(In)-18(div)-16.8(id)-13.7(ua)-10.6(l)-513.5(C)0(d)-10.8(8)0(+)-521.3(T)-512.3(Ce)-9(ll)-14(s)-512.9(R)0(e)-13.2(spo)-14.4(n)-10.8(d)0(i)-13.7(n)0(g)-512.8(t)-7.9(o)-512.9(I)0(n)-10.4(f)-11.4(ec)-14.6(tio)-11.4(n)-10.8(.)]TJ /F11 1 Tf 0 -1.2699 TD (Immunity)Tj /F6 1 Tf 4.2709 0 TD [(\(2013\))-300.7(39\(2\):347)]TJ /F8 1 Tf 6.6823 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(56.)-298(doi:)-301.1(10.1016/j.immuni.2013.07.014)]TJ -13.1454 -1.2699 TD [(27.)-502.1(Fiege)-243.1(JK,)-237.8(Stone)-237.3(IA,)-236(Fay)-240.4(EJ,)-243.5(Markman)-237.8(MW,)-234.5(Wijeyesinghe)-248.1(S,)-236.2(Macchietto)-236.7(MG,)]TJ 1.6781 -1.2624 TD [(et)-506.6(al)-8.4(.)-500.1(The)-510.2(Impac)-14.3(t)-499.3(o)0(f)-509.2(Tcr)-510.9(Sign)-11.6(al)-499.8(St)-8.6(reng)-12.5(th)-505(on)-501.1(Res)-12(ident)-508.4(Mem)-11.1(ory)-507.3(T)-504.8(C)0(e)-8.9(l)0(l)]TJ 0 -1.2699 TD 0.023 Tc [(Formation)-517(D)-3.9(u)6.3(r)1.5(in)4.6(g)-524.4(I)0.7(n)]TJ /F7 1 Tf 9.396 0 TD 0 Tc ()Tj /F6 1 Tf 0.5518 0 TD 0.0226 Tc [(uen)4.2(z)0.2(a)-523.1(V)1.5(irus)-520.5(In)4.2(fection)4.2(.)]TJ /F11 1 Tf 10.356 0 TD 0.0205 Tc [(J)-521.7(I)-1.8(mmun)-7.9(o)4.7(l)]TJ /F6 1 Tf 5.1931 0 TD 0.0199 Tc [(\(20)-7.6(19\))-521.5(20)-7.6(3)]TJ -25.497 -1.2624 TD 0 Tc (\(4\):936)Tj /F8 1 Tf 2.8271 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(45.)-305.6(doi:)-301.1(10.4049/jimmunol.1900093)]TJ -5.0117 -1.2699 TD [(28.)-502.1(Kavazovic)-487.4(I,)-477(Han)-484.4(H,)-473.3(Balzaretti)-488.8(G,)-480(Slinger)-478.3(E,)-482.4(Lemmermann)-486.2(NAW,)-479.7(Ten)]TJ 1.6781 -1.2624 TD [(Brinke)-476.5(A,)-478.3(et)-476.3(al.)-478.3(Eomes)-475.5(Broadens)-477.8(the)-474.5(Scope)-476.9(of)-478.9(Cd8)-476.7(T-Cell)-476.1(Memory)-473(by)]TJ 34.7721 84.8666 TD [(In)-10.4(hib)-9.2(iti)-9.5(ng)-512.8(A)-8.4(pop)-9.6(tos)-13.2(is)-509.9(in)-506.7(C)-9.2(ells)-519.1(of)-509.2(Low)-514.4(Af)]TJ /F7 1 Tf 17.3029 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(nity)-11.3(.)]TJ /F11 1 Tf 2.298 0 TD [(PL)-13.1(oS)-510.2(Bio)-12.8(l)]TJ /F6 1 Tf 4.6035 0 TD [(\(202)-11.5(0\))-508.4(18)-9.6(\(3)-9.5(\):)]TJ -24.7411 -1.2699 TD [(e3000648.)-306.6(doi:)-301.1(10.1371/journal.pbio.3000648)]TJ -1.6781 -1.2624 TD [(29.)-502.1(King)-350.3(CG,)-353.1(Koehli)-347.7(S,)-357.2(Hausmann)-350.2(B,)-348(Schmaler)-357.7(M,)-348.4(Zehn)-353(D,)-345.6(Palmer)-356.5(E.)-346.3(T)-353.6(Cell)]TJ 1.6781 -1.2699 TD (Af)Tj /F7 1 Tf 0.9146 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(nity)-389.2(Regulates)-388.1(Asymmetric)-392.8(Division,)-393.6(Ef)59.3(fector)-386.9(Cell)-393.4(Dif)63(ferentiation,)-398(and)]TJ -1.4514 -1.2624 TD 0.0584 Tc [(Tissue)-561.2(P)0.6(athology.)]TJ /F11 1 Tf 8.814 0 TD 0.0594 Tc [(Immunit)6.1(y)]TJ /F6 1 Tf 4.9966 0 TD 0.058 Tc [(\(2012)-7.3(\))-559(37\(4\):709)]TJ /F8 1 Tf 7.8162 0 TD 0 Tc ()Tj /F6 1 Tf 0.5745 0 TD 0.0578 Tc [(20.)-563.3(doi:)-563.3(10.1016/)]TJ -22.2012 -1.2699 TD 0 Tc (j.immuni.2012.06.021)Tj -1.6781 -1.2699 TD [(30.)-502.1(Knudson)-256(KM,)-256.8(Goplen)-262.5(NP,)-249.8(Cunningham)-258.9(CA,)-260.7(Daniels)-253.4(MA,)-258.5(Teixeiro)-254.8(E.)-255.6(Low-)]TJ 1.6781 -1.2624 TD (Af)Tj /F7 1 Tf 0.9146 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(nity)-336.3(T)-330.9(Cells)-339.3(Are)-332.1(Programmed)-341.2(to)-331.9(Maintain)-343.3(Normal)-337.4(Primary)-333.6(Responses)]TJ -1.4514 -1.2699 TD [(But)-258(Are)-256.5(Impaired)-253.6(in)-257.3(Their)-256.6(Recall)-255.1(to)-256.3(Low-Af)]TJ /F7 1 Tf 17.4768 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(nity)-253.2(Ligands.)]TJ /F11 1 Tf 5.4048 0 TD [(Cell)-255.7(Rep)]TJ /F6 1 Tf 3.4772 0 TD [(\(2013\))-255.3(4)]TJ -26.8955 -1.2624 TD (\(3\):554)Tj /F8 1 Tf 2.8271 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(65.)-305.6(doi:)-301.1(10.1016/j.celrep.2013.07.008)]TJ -5.0117 -1.2699 TD -0.0389 Tc [(3)-38.9(1)-38.9(.)-541(Cho)-234.3(Y)-3.5(L,)-236.7(Fl)7(ossdo)7.6(r)0.1(f)-239.2(M)-0.5(,)-244.2(K)7.3(retschmer)-234.3(L)0.7(,)-244.2(H)3(ofer)-234.3(T,)-244.2(Bu)4.9(sch)-241.1(D)2.2(H,)-244.2(B)7.4(u)-2.7(chhol)7(z)-242.8(VR.)-236.7(T)0.6(cr)-241.8(S)5.8(i)-5.7(gnal)]TJ 1.6781 -1.2624 TD -0.0398 Tc [(Quality)-473.8(M)6.1(odulates)-477.1(Fate)-470.4(D)-6.2(e)5.8(cisi)-6.6(o)6.6(n)-5.3(s)-469.5(o)-0.9(f)-474.5(S)-2.7(ing)-5.1(l)-1.5(e)-470.4(C)-3.7(d4\()-6.7(+)3.1(\))-475.4(T)-476.5(Cells)-469.5(in)-473.9(a)-479.7(P)0.6(robabilistic)]TJ 0 -1.2699 TD -0.0396 Tc [(Ma)-3.2(nner.)]TJ /F11 1 Tf 3.4243 0 TD -0.0371 Tc [(Cel)5.4(l)-297(Rep)]TJ /F6 1 Tf 3.2958 0 TD -0.0408 Tc [(\(2017\))-302.5(20\(4\))-7.7(:806)]TJ /F8 1 Tf 6.0851 0 TD 0 Tc ()Tj /F6 1 Tf 0.4687 0 TD -0.04 Tc [(18.)-298.2(doi:)-298.2(10)-7(.1016)-7(/j.celrep.2017.07.005)]TJ -14.952 -1.2699 TD 0.0279 Tc [(32.)-502.5(S)4.6(n)2(ook)-518.7(JP)7.8(,)-532.7(K)6(im)-528.3(C,)-525.1(Wil)5.8(l)-1.8(iams)-522.8(MA)4.3(.)-532.7(T)6.9(cr)-522.8(Signal)-523.4(St)4.9(rengt)4.9(h)-529.6(Cont)4.9(rol)5.8(s)-530.3(t)4.9(he)]TJ 1.7613 -1.2624 TD 0 Tc [(Di)-16.4(f)56.7(f)-11.4(er)-13.7(en)-18.1(t)-7.9(i)-12.1(a)-9(t)-7.9(io)-11(n)-517.3(o)0(f)-524.3(C)-9.2(d)-9.1(4)-12.3(\(+)-14.8(\))-518.7(E)0(f)44.2(f)0(e)-11.1(c)-14.9(t)-7.9(o)0(r)-519.3(a)-9(n)-10.8(d)-515.6(Me)-21.8(mo)-10.8(r)-14(y)-517.1(T)-512.3(C)-9.2(el)-14.3(ls)-21(.)]TJ /F11 1 Tf 24.794 0 TD 0.0126 Tc [(Sc)12.6(i)-506.5(I)-2.1(m)12.6(m)2.3(un)12.6(ol)]TJ /F6 1 Tf -24.794 -1.2699 TD 0 Tc [(\(2018\))-300.7(3\(25\):eaas9103.)-303.8(doi:)-301.1(10.1126/sciimmunol.aas9103)]TJ -1.7613 -1.2624 TD [(33.)-502.1(Tubo)-224.4(NJ,)-217.7(Pagan)-218.2(AJ,)-224.3(Taylor)-219.2(JJ,)-218.9(Nelson)-221.2(RW,)-225.8(Linehan)-220.2(JL,)-221.6(Ertelt)-222.9(JM,)-215.3(et)-219.3(al.)-221.3(Single)]TJ 1.6781 -1.2699 TD [(Naive)-343.2(Cd4+)-335.5(T)-338.5(Cells)-339.3(From)-343.9(a)-334(Diverse)-341.7(Repertoire)-340.8(Produce)-345.5(Dif)63(ferent)-338.3(Ef)59.3(fector)]TJ 0 -1.2624 TD [(C)-9.2(e)0(l)-21.9(l)-513.5(T)-13.4(y)-10.7(p)-9.1(e)0(s)-527.7(D)0(u)-20.9(r)0(i)-18.5(n)0(g)-527.9(I)0(n)-18(f)-11.4(ec)-14.6(t)-7.9(i)-12.1(on)-17.3(.)]TJ /F11 1 Tf 12.911 0 TD [(Ce)-15.6(l)-10.5(l)]TJ /F6 1 Tf 2.041 0 TD 0.0147 Tc [(\(2)14.7(013)14.7(\))-508.8(15)14.7(3\()14.7(4\):)5.9(7)14.7(85)]TJ /F8 1 Tf 7.5214 0 TD 0 Tc ()Tj /F6 1 Tf 0.514 0 TD [(9)-12.3(6)0(.)-527.6(d)-9.1(oi)-18.6(:)-515.2(1)-12.3(0)-12.3(.)-8.8(10)-17.1(16)-17.1(/)]TJ -22.9874 -1.2699 TD (j.cell.2013.04.007)Tj -1.6781 -1.2699 TD [(34.)-502.1(Pfeif)58.7(fer)-350.1(C,)-343(Stein)-348.8(J,)-344.4(Southwood)-350(S,)-349.6(Ketelaar)-347.9(H,)-344.8(Sette)-348.6(A,)-349.8(Bottomly)-344.7(K.)-348.1(Altered)]TJ 1.6781 -1.2624 TD [(Peptide)-375.4(Ligands)-381.3(Can)-376.7(Control)-371.7(Cd4)-378.4(T)-368.7(Lymphocyte)-377.6(Dif)55.4(ferentiation)]TJ /F11 1 Tf 26.9257 0 TD [(In)-375.7(Vivo)]TJ /F6 1 Tf 3.0841 0 TD (.)Tj /F11 1 Tf -30.0098 -1.2699 TD [(J)-300.3(Exp)-300.1(Med)]TJ /F6 1 Tf 4.4826 0 TD [(\(1995\))-300.7(181\(4\):1569)]TJ /F8 1 Tf 7.6423 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(74.)-298(doi:)-308.6(10.1084/jem.181.4.1569)]TJ -14.317 -1.2624 TD [(35.)-502.1(Bhattacharyya)-248.4(ND,)-234(Feng)-242(CG.)-239.7(Regulation)-245(of)-237(T)-240.2(Helper)-244.7(Cell)-234.6(Fate)-245(by)-236.4(Tcr)-238.8(Signal)]TJ 1.6781 -1.2699 TD (Strength.)Tj /F11 1 Tf 3.9081 0 TD [(Front)-301.9(Immunol)]TJ /F6 1 Tf 6.448 0 TD [(\(2020\))-308.2(11:624.)-298.5(doi:)-301.1(10.3389/)]TJ /F7 1 Tf 11.2556 0 TD ()Tj /F6 1 Tf 0.5367 0 TD (mmu.2020.00624)Tj -23.8264 -1.2624 TD [(36.)-502.1(Solouki)-339(S,)-342(Huang)-337.9(W,)-340.9(Elmore)-338.8(J,)-336.9(Limper)-339.8(C,)-343(Huang)-337.9(F,)-335.4(August)-346.5(A.)-334.7(Tcr)-337(Signal)]TJ 1.6781 -1.2699 TD [(Strength)-261.5(and)-263.3(Antigen)-264.6(Af)]TJ /F7 1 Tf 9.7891 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(nity)-260.7(Regulate)-260.7(Cd8\(+\))-269.4(Memory)-261.4(T)-262.9(Cells.)]TJ /F11 1 Tf 15.6626 0 TD [(J)-262.5(Immunol)]TJ /F6 1 Tf 7.4999 0 0 7.4999 323.2062 455.4141 Tm [(\(2020\))-300.7(205\(5\):1217)]TJ /F8 1 Tf 7.6423 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(27.)-298(doi:)-301.1(10.4049/jimmunol.1901167)]TJ -9.8345 -1.2624 TD [(37.)-502.1(van)-400.9(Gisbergen)-395.1(KP,)-398.4(Klarenbeek)-403.3(PL,)-397.4(Kragten)-399(NA,)-396.9(Unger)-394.7(PP,)-396.6(Nieuwenhuis)]TJ 1.6781 -1.2699 TD [(MB,)-453.2(Wensveen)-453.2(FM,)-455.7(et)-446.1(al.)-455.6(The)-449.7(Costimulatory)-450.8(Molecule)-459.1(Cd27)-451.2(Maintains)]TJ 0 -1.2624 TD [(Clonally)-210.8(Diverse)-213.2(Cd8\(+\))-208.9(T)-210(Cell)-204.4(Responses)-209.7(of)-214.4(Low)-204.5(Antigen)-211.7(Af)]TJ /F7 1 Tf 24.0532 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(nity)-215.4(to)-203.4(Protect)]TJ -24.5824 -1.2699 TD 0.017 Tc [(Against)-512.5(V)-4.1(iral)-511.6(Variants.)]TJ /F11 1 Tf 10.5828 0 TD 0.0145 Tc [(Im)-5.8(mu)-6.3(nity)]TJ /F6 1 Tf 4.6111 0 TD 0.013 Tc [(\()-6.8(2)-6.9(01)-6.9(1\))-520.9(3)-6.9(5)0.7(\()-6.8(1)-6.9(\):9)-6.9(7)]TJ /F8 1 Tf 6.6521 0 TD 0 Tc ()Tj /F6 1 Tf 0.5291 0 TD 0.0192 Tc [(10)6.8(8.)-511.1(doi)7.1(:)-518.7(1)6.8(0)-0.7(.1)6.9(01)6.9(6/)]TJ -22.3751 -1.2624 TD 0 Tc (j.immuni.2011.04.020)Tj -1.6781 -1.2699 TD [(38)-9.6(.)-500.1(A)-8.4(ndar)-12.7(gac)-11.8(hew)-515.2(R,)-506(Mar)-14.8(tinez)-514.1(RJ,)-516.6(Kol)-12.7(awol)-10.7(e)-506.2(EM,)-512(Eva)-9.5(vo)-9.6(ld)-507.5(BD)-10.8(.)-507.7(Cd4)-506.9(T)-512.3(Cell)]TJ 1.6857 -1.2699 TD 0.0236 Tc (Af)Tj /F7 1 Tf 0.96 0 TD 0 Tc ()Tj /F6 1 Tf 0.5518 0 TD 0.0214 Tc [(nity)-518.4(Dive)6.5(rsi)-5.8(t)5.9(y)-526(Is)-514.1(E)-6.2(q)2.3(ually)-518.4(Maintained)-524.4(Duri)-5.9(ng)-518.4(Acut)5.9(e)-522.6(a)-2.7(nd)-524.4(Chronic)]TJ -1.5118 -1.2624 TD 0 Tc (Infection.)Tj /F11 1 Tf 4.1273 0 TD [(J)-300.3(Immunol)]TJ /F6 1 Tf 4.5808 0 TD [(\(2018\))-300.7(201\(1\):19)]TJ /F8 1 Tf 6.6823 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(30.)-298(doi:)-301.1(10.4049/jimmunol.1800295)]TJ -17.5901 -1.2699 TD [(39.)-502.1(Zehn)-224.5(D,)-217.1(Lee)-216.9(SY,)-223.5(Bevan)-218.2(MJ.)-222.9(Complete)-225(But)-220.2(Curtailed)-220.8(T-Cell)-219.1(Response)-226(to)-218.5(Very)]TJ 1.6781 -1.2624 TD 0.0257 Tc [(Lo)4.1(w-Af)]TJ /F7 1 Tf 3.1219 0 TD 0 Tc ()Tj /F6 1 Tf 0.5594 0 TD 0.0221 Tc [(nity)-525.3(Antige)-7.9(n.)]TJ /F11 1 Tf 6.3195 0 TD 0.0225 Tc [(Natu)-5.9(re)]TJ /F6 1 Tf 3.447 0 TD 0.0199 Tc [(\()-7.5(2)0(0)-7.6(0)0(9)-7.6(\))-529.1(45)-7.6(8\()-7.5(72)-7.6(35)-7.6(\):)-11.5(21)-7.6(1)]TJ /F8 1 Tf 9.2751 0 TD 0 Tc ()Tj /F6 1 Tf 0.5367 0 TD 0.0213 Tc [(4.)-531.7(doi)-6(:)-524.2(1)-6.2(0)1.4(.1)-6.2(03)-6.2(8/)]TJ -23.2595 -1.2699 TD 0 Tc (nature07657)Tj -1.6781 -1.2624 TD [(40.)-502.1(Denton)-297(AE,)-294.3(Wesselingh)-300(R,)-294.3(Gras)-296.5(S,)-296.7(Guillonneau)-303(C,)-297.7(Olson)-289.5(MR,)-301.3(Mintern)-296.7(JD,)]TJ 1.6781 -1.2699 TD [(et)-385.6(al.)-387.6(Af)]TJ /F7 1 Tf 3.3109 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(nity)-381.7(Thresholds)-391.4(for)-387.1(Naive)-388.6(Cd8+)-388.4(Ctl)-387(Activation)-387.6(by)-380(Peptides)-396.9(and)]TJ -3.8476 -1.2699 TD 0.0221 Tc [(Engineered)-523.7(In)]TJ /F7 1 Tf 6.1531 0 TD 0 Tc ()Tj /F6 1 Tf 0.5518 0 TD 0.0224 Tc [(uenza)-515.7(a)-523.3(Viruses.)]TJ /F11 1 Tf 7.8464 0 TD 0.0211 Tc [(J)-521.1(I)-1.2(mm)-6.7(unol)]TJ /F6 1 Tf 5.1931 0 TD 0.0201 Tc [(\(2)-7.4(011\))-528.9(187\()-7.3(11\):57)-7.4(3)0.2(3)]TJ /F8 1 Tf 8.7308 0 TD 0 Tc ()Tj /F6 1 Tf 0.5367 0 TD 0.0199 Tc (44.)Tj -29.012 -1.2624 TD 0 Tc [(doi:)-301.1(10.4049/jimmunol.1003937)]TJ -1.6781 -1.2699 TD [(41.)-502.1(Schober)-206.6(K,)-204.5(Voit)-206.4(F,)-206.9(Grassmann)-201.8(S,)-206(Muller)-210.1(TR,)-201.9(Eggert)-206.6(J,)-200.8(Jarosch)-210.6(S,)-206(et)-204.2(al.)-198.6(Reverse)]TJ 1.6781 -1.2624 TD [(Tcr)-412.6(Repertoire)-408.8(Evolution)-408.1(Toward)-410.5(Dominant)-405.9(Low-Af)]TJ /F7 1 Tf 21.7174 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(nity)-411.9(Clones)-410(During)]TJ -22.2466 -1.2699 TD [(Chronic)-383(Cmv)-387.1(Infection.)]TJ /F11 1 Tf 10.1671 0 TD [(Nat)-386.7(Immunol)]TJ /F6 1 Tf 5.9264 0 TD [(\(2020\))-383.8(21\(4\):434)]TJ /F8 1 Tf 6.7654 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(41.)-381.2(doi:)-384.2(10.1038/)]TJ -23.3729 -1.2624 TD (s41590-020-0628-2)Tj -1.6781 -1.2699 TD [(42.)-502.1(Grassmann)-232(S,)-228.7(Mihatsch)-227.4(L,)-226.1(Mir)-229.6(J,)-231(Kazeroonian)-228.5(A,)-228.9(Rahimi)-230.6(R,)-226.3(Flommersfeld)-229.9(S,)]TJ 1.6781 -1.2699 TD [(et)-355.4(al.)-364.9(Early)-355.5(Emergence)-361.2(of)-358(T)-361.1(Central)-360(Memory)-359.7(Precursors)-361.9(Programs)-357(Clonal)]TJ 0 -1.2624 TD 0.0163 Tc [(D)4.5(o)-5.3(m)4.3(i)4.2(na)7.3(nce)-512.6(D)4.5(uri)4.2(n)-2.1(g)-508.4(C)-0.5(h)3(roni)4.2(c)-512.6(Viral)-504.7(I)1.6(nf)4.9(ection)5.5(.)]TJ /F11 1 Tf 19.7294 0 TD 0.0147 Tc [(Nat)-514.8(I)14.7(m)-12.7(m)2(unol)]TJ /F6 1 Tf 6.327 0 TD 0.0123 Tc [(\(202)-7.6(0)-0.1(\))-514(2)-7.6(1)]TJ -26.0564 -1.2699 TD 0 Tc (\(12\):1563)Tj /F8 1 Tf 3.7796 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(73.)-298(doi:)-301.1(10.1038/s41590-020-00807-y)]TJ -5.9717 -1.2624 TD [(4)-12.3(3)0(.)-512.5(E)-12.5(ll)-14(i)-12.1(o)0(t)-528.4(T)0(A)-14.3(E)-12.5(,)-515.2(J)-10.6(en)-18.1(ni)-15.4(n)-10.8(g)0(s)-523.5(E)-12.5(K,)-522(L)-13.3(e)0(c)-14.6(k)-9.9(y)-517.1(D)-11.8(A)-8.4(J)0(,)-525.8(T)0(h)-11.5(a)-9(w)-10.9(a)-9(i)-12.1(t)-514.4(N)-9.4(,)-515.2(F)-9.1(l)0(o)-21(r)0(e)-13.7(s)-14(-)-8.9(L)0(a)-14.7(n)-10.8(ga)-12.1(r)-14(i)0(c)-19.4(a)-515.5(A)-8.4(,)]TJ 1.7008 -1.2699 TD 0.0403 Tc [(C)-6.7(o)3.6(pl)-4.5(and)-543.3(A)1.6(,)-543(e)-4.8(t)-542.1(a)1.1(l.)-543(Ant)-5.4(i)-2.1(gen)-545(a)1.1(nd)-543.3(Chec)-4.8(kpoint)-542.1(Re)-4.8(ce)-4.8(ptor)-540.6(Engageme)-4.8(nt)]TJ 0 -1.2624 TD 0.0363 Tc [(Rec)6.3(a)-2.9(l)6.6(i)1.5(bra)4.6(t)5.7(es)-529.5(T)-536.5(C)4.4(el)6.6(l)-530.1(R)0.2(ec)6.3(ep)4.5(to)7.2(r)-529.5(S)-2.2(igna)4.6(l)-537.6(S)5.4(tr)7.2(engt)5.7(h.)]TJ /F11 1 Tf 21.0976 0 TD [(Imm)8.4(unity)]TJ /F6 1 Tf 4.7774 0 TD 0.035 Tc [(\(2)7.5(021\))-536.7(5)7.5(4)]TJ -25.875 -1.2699 TD 0 Tc (\(11\):2481)Tj /F8 1 Tf 3.7871 0 TD ()Tj /F6 1 Tf 0.5065 0 TD 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TD [(nity-Mediated)-368.7(Metabolic)]TJ -20.2207 -1.2699 TD [(Programming)-411.2(and)-406.9(Clonal)-404.7(Expansion)-410.5(of)-403.3(T)-406.5(Cells.)]TJ /F11 1 Tf 20.2963 0 TD [(Nat)-409.3(Immunol)]TJ /F6 1 Tf 5.9642 0 TD [(\(2013\))-406.5(14)]TJ -26.2605 -1.2624 TD (\(11\):1155)Tj /F8 1 Tf 3.7796 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(65.)-298(doi:)-308.6(10.1038/ni.2710)]TJ -5.9717 -1.2699 TD [(59.)-502.1(Nayar)-225.8(R,)-226.3(Schutten)-223.1(E,)-225.4(Bautista)-226.8(B,)-219.5(Daniels)-230.7(K,)-219.6(Prince)-230.3(AL,)-219.4(Enos)-225.1(M,)-227.4(et)-219.3(al.)-221.3(Graded)]TJ 1.6781 -1.2624 TD [(Levels)-278.7(of)-267.3(Irf4)-271.6(Regulate)-275.8(Cd8+)-275.1(T)-270.4(Cell)-272.4(Dif)63(ferentiation)-275.8(and)-270.8(Expansion,)-275.6(But)-273.1(Not)]TJ 0 -1.2699 TD [(Attrition,)-482(in)-476.5(Response)-475.4(to)-475.5(Acute)-478.5(Virus)-478.5(Infection.)]TJ /F11 1 Tf 20.7801 0 TD [(J)-481.7(Immunol)]TJ /F6 1 Tf 4.9361 0 TD [(\(2014\))-474.5(192)]TJ -25.7162 -1.2699 TD (\(12\):5881)Tj /F8 1 Tf 3.7796 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(93.)-298(doi:)-308.6(10.4049/jimmunol.1303187)]TJ -5.9717 -1.2624 TD [(60.)-502.1(Preston)-277(GC,)-270(Sinclair)-277.1(LV,)-277.5(Kaskar)-274.2(A,)-274.2(Hukelmann)-275.9(JL,)-274.5(Navarro)-268.9(MN,)-274.5(Ferrero)-276.2(I,)]TJ 1.6781 -1.2699 TD [(et)-423.4(al.)-425.4(Single)-426.5(Cell)-423.6(Tuning)-422.2(of)-426(Myc)-418(Expression)-433.5(by)-417.8(Antigen)-430.9(Receptor)-420.5(Signal)]TJ 0 -1.2624 TD [(Strength)-253.9(and)-255.7(Interleukin-2)-253.1(in)-257.3(T)-247.7(Lymphocytes.)]TJ /F11 1 Tf 7.4999 0 0 7.4999 201.9968 293.9527 Tm [(EMBO)-252(J)]TJ /F6 1 Tf 3.515 0 TD [(\(2015\))-255.3(34\(15\):2008)]TJ /F8 1 Tf 7.5969 0 TD ()Tj /F6 1 Tf -29.7226 -1.2699 TD [(24.)-305.6(doi:)-301.1(10.15252/embj.201490252)]TJ -1.6781 -1.2624 TD [(61.)-502.1(Yao)-486.5(S,)-478.1(Buzo)-483.1(BF,)-485.6(Pham)-485.1(D,)-481.7(Jiang)-484.1(L,)-483.1(Taparowsky)-484.3(EJ,)-485.4(Kaplan)-482.6(MH,)-480.3(et)-483.9(al.)]TJ 1.6781 -1.2699 TD [(In)-10.4(ter)-14.1(fer)-10(on)-516.2(Regu)-17.8(la)-8.4(tory)-515.2(Fa)-10.6(cto)-14.1(r)-505.3(4)-503.7(Su)-9.8(st)-14.3(ain)-9.3(s)-505.3(C)-9.2(d8\()-11.1(+\))-513.7(T)-504.8(C)-9.2(ell)-512.7(Exp)-14.7(ans)-11.1(io)-11(n)-502.2(a)-9(nd)]TJ T* 0.0203 Tc [(Ef)69.4(fe)5.4(ct)4.8(o)6.3(r)-515.2(D)8.5(i)0.6(f)69.4(f)1.4(er)6.3(e)5.4(n)1.9(t)4.8(i)0.6(a)3.7(t)4.8(io)6.3(n.)]TJ /F11 1 Tf 10.5828 0 TD 0.0145 Tc [(Im)-5.8(mu)-6.3(nity)]TJ /F6 1 Tf 4.6186 0 TD 0.0123 Tc [(\(2)-7.6(01)-7.6(3)-7.6(\))-521.6(39)-7.6(\(5)-7.6(\):)-11.6(83)-7.6(3)]TJ /F8 1 Tf 7.1434 0 TD 0 Tc ()Tj /F6 1 Tf 0.5291 0 TD 0.0193 Tc [(4)7(5)-0.6(.)-511.1(d)-5(o)5.3(i)7.2(:)-518.6(1)7(0.10)7(16)7(/)]TJ -22.874 -1.2624 TD 0 Tc (j.immuni.2013.10.007)Tj -1.6781 -1.2699 TD [(62.)-502.1(Allison)-322.8(KA,)-326.3(Sajti)-324(E,)-323.6(Collier)-320.1(JG,)-324.3(Gosselin)-323.6(D,)-322.9(Troutman)-324.5(TD,)-321.2(Stone)-320.4(EL,)-329.3(et)-317.6(al.)]TJ 1.6781 -1.2624 TD (Af)Tj /F7 1 Tf 0.9222 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(nity)-200.3(and)-202.8(Dose)-198.2(of)-199.2(Tcr)-201(Engagement)-204.7(Yield)-204.3(Proportional)-206.5(Enhancer)-205.9(and)-202.8(Gene)]TJ -1.4514 -1.2699 TD [(Activity)-273.7(in)-272.4(Cd4+)-275.1(T)-270.4(Cells.)]TJ /F11 1 Tf 10.3031 0 TD (Elife)Tj /F6 1 Tf 1.9956 0 TD [(\(2016\))-270.4(5:e10134.)-272.7(doi:)-270.8(10.7554/eLife.10134)]TJ -13.9769 -1.2624 TD [(63.)-502.1(van)-461.3(Panhuys)-464.8(N,)-456.6(Klauschen)-462.5(F,)-456.3(Germain)-468.3(RN.)-454.8(T-Cell-Receptor-Dependent)]TJ 1.6781 -1.2699 TD [(Signal)-352.6(Intensity)-345.7(Dominantly)-348(Controls)-347.9(Cd4\(+\))-345(T)-346(Cell)-348(Polarization)-349(in)-348(Vivo.)]TJ /F11 1 Tf T* (Immunity)Tj /F6 1 Tf 4.2709 0 TD [(\(2014\))-300.7(41\(1\):63)]TJ /F8 1 Tf 6.2061 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(74.)-298(doi:)-301.1(10.1016/j.immuni.2014.06.003)]TJ -12.6691 -1.2624 TD [(64.)-502.1(Tan)-207.1(TCJ,)-200.7(Knight)-205.2(J,)-208.4(Sbarrato)-203.4(T,)-203.6(Dudek)-206(K,)-204.5(Willis)-203(AE,)-203.6(Zamoyska)-203.5(R.)-203.6(Suboptimal)]TJ 1.6781 -1.2699 TD [(T-C)-8.8(ell)-505.1(Rec)-12.9(ept)-9.2(or)-504.2(Sign)-11.6(aling)-510.7(Co)-8.1(mpromi)-12.6(ses)-511.4(Prot)-10.6(ein)-506.5(Trans)-15.8(lation,)-515.6(Rib)-9.3(osome)]TJ 0 -1.2624 TD [(Biogenesis,)-442.7(and)-437.1(Proliferation)-433.3(of)-433.6(Mouse)-436.9(Cd8)-438.9(T)-429.2(Cells.)]TJ /F11 1 Tf 22.3146 0 TD [(Proc)-433.1(Natl)-434.9(Acad)-436.7(Sci)]TJ -22.3146 -1.2699 TD (USA)Tj /F6 1 Tf 2.1166 0 TD [(\(2017\))-300.7(114\(30\):E6117)]TJ /F8 1 Tf 8.6855 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(E26.)-302.9(doi:)-301.1(10.1073/pnas.1700939114)]TJ -12.9866 -1.2624 TD [(65.)-502.1(Salerno)-365.1(F,)-365.6(Turner)-370.9(M,)-363.5(Wolkers)-368.1(MC.)-365.1(Dynamic)-360.9(Post-Transcriptional)-372.9(Events)]TJ 1.6781 -1.2699 TD [(G)-10.1(o)-14(v)-10.7(e)0(r)-21.3(n)-10.8(i)-12.1(n)-10.8(g)-517.1(C)-16.8(d)-9.1(8)-12.3(\(+)-22.3(\))-518.7(T)-519.9(C)-9.2(e)-14.9(ll)-528(H)-11(o)-14(m)-11.9(e)0(o)-21.3(s)0(t)-21.9(a)-9(si)-18.5(s)-520.4(a)-16.5(n)-10.8(d)-515.6(E)-12.5(f)49.1(f)-11.4(e)0(c)-22.2(t)-7.9(o)-14(r)-520.4(F)-9.1(u)-9.1(n)-10.8(c)-14.9(t)-7.9(i)-12.1(o)-14(n)-10.8(.)]TJ /F11 1 Tf 27.4548 0 TD 0.013 Tc [(Tren)13(d)-6.7(s)]TJ -27.4548 -1.2699 TD 0 Tc (Immunol)Tj /F6 1 Tf 3.9686 0 TD [(\(2020\))-300.7(41\(3\):240)]TJ /F8 1 Tf 6.6823 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(54.)-298(doi:)-301.1(10.1016/j.it.2020.01.001)]TJ -12.843 -1.2624 TD [(66.)-502.1(Moreau)-302.3(HD,)-303.7(Lemaitre)-302(F,)-297.6(Terriac)-303.8(E,)-293.4(Azar)-303.2(G,)-298.6(Piel)-303.5(M,)-295.4(Lennon-Dumenil)-304.7(AM,)]TJ 1.6781 -1.2699 TD [(et)-204.2(al.)-206.2(Dynamic)-209.7(in)-204.4(Situ)-203.7(Cytometry)-207(Uncovers)-203.2(T)-209.9(Cell)-204.4(Receptor)-201.3(Signaling)-212.4(During)]TJ 0 -1.2624 TD [(Immunological)-215.3(Synapses)-219.1(and)-217.9(Kinapses)]TJ /F11 1 Tf 15.587 0 TD [(In)-217(Vivo)]TJ /F6 1 Tf 2.9254 0 TD (.)Tj /F11 1 Tf 0.4309 0 TD (Immunity)Tj /F6 1 Tf 4.1802 0 TD [(\(2012\))-210(37\(2\):351)]TJ /F8 1 Tf 6.5991 0 TD ()Tj /F6 1 Tf -29.7226 -1.2699 TD [(63.)-305.6(doi:)-301.1(10.1016/j.immuni.2012.05.014)]TJ 33.094 83.6042 TD [(67.)-502.1(Ozga)-323.6(AJ,)-322.6(Moalli)-313.1(F,)-320.3(Abe)-324.6(J,)-321.7(Swoger)-314.5(J,)-321.7(Sharpe)-325.4(J,)-321.7(Zehn)-315.2(D,)-322.9(et)-317.6(al.)-319.6(Pmhc)-324.7(Af)]TJ /F7 1 Tf 29.8133 0 TD ()Tj /F6 1 Tf 0.5291 0 TD (nity)Tj -28.6643 -1.2699 TD [(Controls)-287.4(Duration)-292.8(of)-282.4(Cd8+)-290.2(T)-285.5(Cell-Dc)-292.8(Interactions)-288.6(and)-293.5(Imprints)-283.5(Timing)-290.3(of)]TJ 0 -1.2624 TD [(Ef)59.3(fector)-281.1(Dif)63(ferentiation)-283.4(Versus)-283.5(Expansion.)]TJ /F11 1 Tf 17.1971 0 TD [(J)-277.6(Exp)-284.9(Med)]TJ /F6 1 Tf 4.4221 0 TD [(\(2016\))-278(213\(12\):2811)]TJ /F8 1 Tf 8.0959 0 TD ()Tj /F6 1 Tf -29.715 -1.2699 TD [(29.)-305.6(doi:)-301.1(10.1084/jem.20160206)]TJ -1.6781 -1.2624 TD [(68.)-502.1(Skokos)-236.3(D,)-232.2(Shakhar)-235.3(G,)-230.5(Varma)-238.8(R,)-226.3(Waite)-240(JC,)-232.7(Cameron)-235(TO,)-228.1(Lindquist)-236.1(RL,)-232(et)-234.4(al.)]TJ 1.6781 -1.2699 TD [(Peptide-Mhc)-336.1(Potency)-335.1(Governs)-330.3(Dynamic)-338.2(Interactions)-333.9(Between)-330.3(T)-338.5(Cells)-331.7(and)]TJ T* 0.022 Tc [(Dend)5.3(r)-7.1(i)2.3(tic)-522(C)5.2(ells)-521.1(in)-518(L)-6.4(y)3.8(mph)-520.4(N)-2.5(od)5.3(es.)]TJ /F11 1 Tf 15.3451 0 TD 0.0215 Tc [(Nat)-515.6(I)-0.8(mmun)-6.9(o)5.7(l)]TJ /F6 1 Tf 6.4102 0 TD 0.0202 Tc [(\(200)-7.3(7\))-521.2(8\(8)-7.3(\))0.4(:835)]TJ /F8 1 Tf 6.7201 0 TD 0 Tc ()Tj /F6 1 Tf 0.5367 0 TD 0.0199 Tc (44.)Tj -29.012 -1.2624 TD 0 Tc [(doi:)-301.1(10.1038/ni1490)]TJ -1.6781 -1.2699 TD [(69.)-502.1(Jennings)-321.4(E,)-308.5(Elliot)-317.6(TAE,)-315.2(Thawait)-309.9(N,)-312.9(Kanabar)-321.9(S,)-311.8(Yam-Puc)-318.1(JC,)-308.3(Ono)-313.9(M,)-318.1(et)-310(al.)]TJ 1.6781 -1.2624 TD [(Nr4a1)-510.5(and)-505.2(Nr4a3)-510.5(Repo)-13.6(rter)-504.2(Mice)-509.9(Are)-505.9(Dif)55.4(feren)-13(tially)-507.3(Sensit)-15(ive)-506.3(to)-498.2(T)-504.8(Cell)]TJ 0 -1.2699 TD [(Re)-20.7(ce)-14.6(p)-9.1(t)0(o)-14.4(r)-512.9(Si)-12.8(g)-10.7(n)0(a)-12.2(l)-513.5(St)-16.1(re)-21.3(ng)-13.9(t)-7.9(h)-512.2(a)-9(n)-10.8(d)-508(D)-11.8(u)-9.1(r)0(a)-15.4(t)-7.9(io)-11(n)-10.8(.)]TJ /F11 1 Tf 17.5146 0 TD [(Ce)-15.6(ll)-519.8(R)-11.7(e)0(p)]TJ /F6 1 Tf 4.029 0 TD [(\()-12.3(2)0(0)-17.1(2)0(0)-9.6(\))-518.7(33)-17.1(\(5)-9.5(\))-12.3(:)-8.8(10)-9.6(8)-12.4(3)0(2)-9.6(8)-12.3(.)]TJ -21.5436 -1.2624 TD [(doi:)-301.1(10.1016/j.celrep.2020.108328)]TJ -1.6781 -1.2699 TD [(7)-12.3(0)0(.)-520(H)0(a)-20(r)0(r)-12.8(i)-12.1(s)-520.4(M)0(J)-17.6(,)-515.2(F)-9.1(u)-9.1(y)-10.7(a)-9(l)-521(M,)-529.8(J)-10.6(a)-9(me)-19.2(s)-512.9(J)-10.6(R)-13.4(.)-515.2(Q)-9.4(u)-9.1(a)-9(n)-10.8(t)-7.9(i)-12.1(f)-11.4(y)0(i)-15.2(n)-10.8(g)-517.1(P)-12.5(er)-13.7(s)-14(i)0(s)-18.5(t)-7.9(en)-18.1(ce)-528.6(in)-529.4(t)-7.9(h)0(e)-527(T)0(-)-14.7(C)-9.2(e)-14.9(l)0(l)]TJ 1.7084 -1.2699 TD [(Signaling)-318.2(Network)-322.8(Using)-316.3(an)-314.6(Optically)-321.4(Controllable)-317.8(Antigen)-325.1(Receptor.)]TJ /F11 1 Tf 28.6189 0 TD (Mol)Tj -28.6189 -1.2624 TD [(Syst)-299.3(Biol)]TJ /F6 1 Tf 3.6813 0 TD [(\(2021\))-300.7(17\(5\):e10091.)-306.9(doi:)-301.1(10.15252/msb.202010091)]TJ -5.3897 -1.2699 TD [(71.)-502.1(Blair)-230.1(DA,)-225.5(Turner)-234.9(DL,)-230.4(Bose)-230.9(TO,)-228.1(Pham)-228.1(QM,)-229.2(Bouchard)-233.6(KR,)-225.5(Williams)-231.4(KJ,)-230.2(et)-226.9(al.)]TJ 1.6781 -1.2624 TD [(Duration)-444(of)-448.7(Antigen)-446(Availability)-445.1(In)]TJ /F7 1 Tf 14.8688 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(uences)-441.3(the)-444.2(Expansion)-448.3(and)-444.7(Memory)]TJ -15.398 -1.2699 TD [(Dif)63(ferentiation)-328.8(of)-320.2(T)-323.3(Cells.)]TJ /F11 1 Tf 10.6962 0 TD [(J)-323(Immunol)]TJ /F6 1 Tf 4.6262 0 TD [(\(2011\))-323.4(187\(5\):2310)]TJ /F8 1 Tf 7.665 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(21.)-320.7(doi:)-323.7(10.4049/)]TJ -23.4938 -1.2624 TD (jimmunol.1100363)Tj -1.6781 -1.2699 TD [(7)-12.3(2)-12.3(.)-507.7(P)-12.5(r)0(l)-21(i)0(c)-525.9(M)0(,)-529.8(H)-11(er)-21.3(n)-10.8(a)-9(n)-10.8(d)-9.1(ez)-22.2(-)-8.8(H)-11(oy)-17.1(os)-526.9(G)-10.1(,)-522.8(Be)-21.5(v)-10.7(a)-9(n)-517.3(M)-14.5(J)-10.6(.)-515.2(D)-11.8(u)-9.1(r)-14(a)-9(t)-7.9(i)-12.1(on)-523.7(o)-14(f)-517.8(t)-7.9(h)-13.3(e)-521.3(I)0(n)-18(i)-12.1(t)-7.9(i)-12.1(a)-9(l)-521(Tc)-20.7(r)]TJ 1.7084 -1.2699 TD [(Stimulus)-449.8(Controls)-453.7(the)-444.2(Magnitude)-453.5(But)-454.5(Not)-447(Functionality)-453(of)-448.7(the)-451.8(Cd8+)-448.9(T)]TJ 0 -1.2624 TD [(Cell)-204.4(Response.)]TJ /F11 1 Tf 5.9339 0 TD [(J)-202(Exp)-201.8(Med)]TJ /F6 1 Tf 4.1802 0 TD [(\(2006\))-202.4(203\(9\):2135)]TJ /F8 1 Tf 7.5516 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(43.)-199.8(doi:)-202.8(10.1084/jem.20060928)]TJ -19.8806 -1.2699 TD [(73.)-502.1(van)-468.9(Stipdonk)-466.8(MJ,)-464.8(Hardenberg)-470(G,)-464.9(Bijker)-465.1(MS,)-462.4(Lemmens)-469.6(EE,)-464.6(Droin)-463.3(NM,)]TJ 1.6781 -1.2624 TD [(Green)-253.6(DR,)-245.6(et)-242(al.)-251.5(Dynamic)-247.5(Programming)-252.5(of)-244.6(Cd8+)-244.8(T)-247.7(Lymphocyte)-249.1(Responses.)]TJ /F11 1 Tf 0 -1.2699 TD [(Nat)-303.5(Immunol)]TJ /F6 1 Tf 5.7601 0 TD [(\(2003\))-300.7(4\(4\):361)]TJ /F8 1 Tf 6.2061 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(5.)-300.8(doi:)-301.1(10.1038/ni912)]TJ -14.1507 -1.2624 TD [(74.)-502.1(Chang)-249.5(JT,)-259.6(Palanivel)-251.7(VR,)-247.4(Kinjyo)-257.9(I,)-250.3(Schambach)-252(F,)-252.2(Intlekofer)-255.5(AM,)-250.9(Banerjee)-250.7(A,)]TJ 1.6781 -1.2699 TD [(et)-461.2(al.)-455.6(Asymmetric)-468.4(T)-459.4(Lymphocyte)-460.7(Division)-460.5(in)-461.4(the)-459.4(Initiation)-459.3(of)-456.3(Adaptive)]TJ T* 0.0212 Tc [(Immune)-522.8(Re)6.3(spo)7.2(n)-4.7(se)6.3(s.)]TJ /F11 1 Tf 9.1239 0 TD 0.0201 Tc (Science)Tj /F6 1 Tf 3.4621 0 TD [(\(2007\))-521.3(315\(5819\):1687)]TJ /F8 1 Tf 7.4999 0 0 7.4999 490.3369 455.4141 Tm 0 Tc ()Tj /F6 1 Tf 0.5291 0 TD 0.0195 Tc [(91.)-526(doi:)-518.4(10)-8(.1126/)]TJ -22.8135 -1.2624 TD 0 Tc (science.1139393)Tj -1.6781 -1.2699 TD [(75.)-502.1(Arsenio)-314.9(J,)-314.2(Metz)-316.8(PJ,)-311.6(Chang)-317.5(JT.)-312.5(Asymmetric)-317.2(Cell)-317.8(Division)-309.3(in)-317.7(T)-308.2(Lymphocyte)]TJ 1.6781 -1.2624 TD [(Fate)-381.1(Diversi)]TJ /F7 1 Tf 4.9059 0 TD ()Tj /F6 1 Tf 0.5367 0 TD (cation.)Tj /F11 1 Tf 3.0539 0 TD [(Trends)-375.7(Immunol)]TJ /F6 1 Tf 7.1358 0 TD [(\(2015\))-376.3(36\(11\):670)]TJ /F8 1 Tf 7.2417 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(83.)-381.2(doi:)-376.6(10.1016/)]TJ -23.3805 -1.2699 TD (j.it.2015.09.004)Tj -1.6781 -1.2624 TD [(76.)-502.1(Arsenio)-488.8(J,)-488(Kakaradov)-492(B,)-484(Metz)-490.6(PJ,)-485.4(Kim)-491.9(SH,)-489.1(Yeo)-484.8(GW,)-487.1(Chang)-483.8(JT.)-493.9(Early)]TJ 1.6781 -1.2699 TD (Speci)Tj /F7 1 Tf 2.0863 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(cation)-507.2(of)-501.6(Cd8+)-501.8(T)-497.2(Lymphocyte)-506.1(Fates)-500.9(During)-506.9(Adaptive)-504.6(Immunity)]TJ -2.6155 -1.2699 TD [(Revealed)-449.1(by)-448(Single-Cell)-443.2(Gene-Expression)-455.1(Analyses.)]TJ /F11 1 Tf 21.5814 0 TD [(Nat)-447.1(Immunol)]TJ /F6 1 Tf 6.0398 0 TD (\(2014\))Tj -27.6211 -1.2624 TD (15\(4\):365)Tj /F8 1 Tf 3.7796 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(72.)-298(doi:)-301.1(10.1038/ni.2842)]TJ -5.9717 -1.2699 TD [(77.)-502.1(Kakaradov)-340.8(B,)-332.9(Arsenio)-330.1(J,)-336.9(Widjaja)-332.5(CE,)-332.8(He)-335.8(Z,)-330.4(Aigner)-335.4(S,)-334.5(Metz)-331.9(PJ,)-334.2(et)-332.7(al.)-334.7(Early)]TJ 1.6781 -1.2624 TD 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-1.6781 -1.2699 TD 0.0143 Tc [(8)-5.6(8)2(.)-500.9(J)3.7(oshi)-511.9(N)-2.6(S,)-516.1(Cui)-511.9(W)-0.4(,)-516.1(C)5.1(handele)-514.6(A)-1.7(,)-508.5(L)-6.5(e)14.3(e)-521.9(HK,)-508.5(U)-5.1(rso)-513.7(DR,)-516.1(H)3.3(agm)-5.2(a)5.3(n)-518.1(J)3.7(,)-516.1(e)-0.6(t)-507.7(a)-2.2(l.)]TJ 1.7235 -1.2624 TD 0 Tc (In)Tj /F7 1 Tf 0.8693 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(ammation)-328.6(Directs)-331.4(Memory)-329.4(Precursor)-340.4(and)-323.7(Short-Lived)-337.9(Ef)59.3(fector)-326.4(Cd8\(+\))]TJ -1.406 -1.2699 TD [(T)-459.4(Cell)-469(Fates)]TJ /F11 1 Tf 5.6164 0 TD (Via)Tj /F6 1 Tf 1.8898 0 TD [(the)-466.9(Graded)-466.8(Expression)-471.2(of)-463.8(T-Bet)-459.8(Transcription)-473.5(Factor.)]TJ /F11 1 Tf -7.5062 -1.2699 TD (Immunity)Tj /F6 1 Tf 4.2634 0 TD [(\(2007\))-308.2(27\(2\):281)]TJ /F8 1 Tf 6.6898 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(95.)-305.6(doi:)-301.1(10.1016/j.immuni.2007.07.010)]TJ -13.1832 -1.2624 TD [(89.)-502.1(Cui)-287.5(W,)-280.5(Joshi)-283.2(NS,)-290.9(Jiang)-280(A,)-289.3(Kaech)-285.5(SM.)-281(Ef)59.3(fects)-282.2(of)-282.4(Signal)-284.6(3)-284.5(During)-287.7(Cd8)-280.1(T)-285.5(Cell)]TJ 1.6781 -1.2699 TD [(Priming:)-259.2(Bystander)-263.2(Production)-262.1(of)-252.2(Il-12)-259.3(Enhances)-258.8(Ef)59.3(fector)-258.4(T)-255.3(Cell)-257.3(Expansion)]TJ 0 -1.2624 TD [(But)-507.5(Promot)-13.9(es)-505(Terminal)-508.8(Di)-8.8(f)64.2(fer)-9.9(entiatio)-13.2(n.)]TJ /F11 1 Tf 17.0534 0 TD (Vaccine)Tj /F6 1 Tf 3.6133 0 TD [(\(200)-11.5(9\))-500.8(27\(15\))-13.4(:2177)]TJ /F8 1 Tf 7.8691 0 TD ()Tj /F6 1 Tf 0.514 0 TD (87.)Tj -29.0498 -1.2699 TD [(doi:)-301.1(10.1016/j.vaccine.2009.01.088)]TJ -1.6781 -1.2624 TD [(90.)-502.1(Takemoto)-344.5(N,)-343.2(Intlekofer)-346.2(AM,)-341.7(Northrup)-347.7(JT,)-342.7(Wherry)-345.9(EJ,)-341.8(Reiner)-344.6(SL.)-347.7(Cutting)]TJ 1.6781 -1.2699 TD [(Edge:)-214.7(Il-12)-214(Inversely)-217.3(Regulates)-214.2(T-Bet)-210.4(and)-210.4(Eomesodermin)-214.6(Expression)-221.8(During)]TJ T* [(Pa)-13.9(t)-7.9(hog)-15.3(en)-10.6(-I)-8.4(n)-10.8(d)0(u)-10.7(ced)-522.7(Cd)-10.8(8+)-513.7(T)-512.3(C)-9.2(ell)-520.2(Di)-8.8(f)56.7(f)0(e)-11.1(r)0(e)-13.7(n)0(t)-11.2(i)0(a)-13.6(t)0(i)-12.5(o)0(n)-9.7(.)]TJ /F11 1 Tf 20.6062 0 TD 0.5119 Tc [(JI)511.9(m)499.6(m)511.9(u)501.1(n)511.9(o)498(l)]TJ /F6 1 Tf 5.0344 0 TD 0 Tc [(\(2)-9.5(00)-9.6(6\))-516(17)-17.1(7)]TJ -25.6406 -1.2624 TD (\(11\):7515)Tj /F8 1 Tf 3.7796 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(9.)-300.8(doi:)-301.1(10.4049/jimmunol.177.11.7515)]TJ -5.9717 -1.2699 TD [(91.)-502.1(Pipkin)-308.5(ME,)-307.9(Sacks)-312.9(JA,)-307.5(Cruz-Guilloty)-307.8(F,)-305.2(Lichtenheld)-312.8(MG,)-305.5(Bevan)-308.9(MJ,)-306(Rao)-308.5(A.)]TJ 1.6781 -1.2624 TD [(Interleukin-2)-336.3(and)-331.3(In)]TJ /F7 1 Tf 8.3075 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(ammation)-336.2(Induce)-330.5(Distinct)-333.4(Transcriptional)-338.4(Programs)]TJ -8.8366 -1.2699 TD [(That)-398.8(Promote)-399.1(the)-398.9(Dif)63(ferentiation)-396.8(of)-395.8(Ef)59.3(fector)-402(Cytolytic)-396.7(T)-391.4(Cells.)]TJ /F11 1 Tf 26.2605 0 TD (Immunity)Tj /F6 1 Tf -26.2605 -1.2624 TD [(\(2010\))-300.7(32\(1\):79)]TJ /F8 1 Tf 6.2061 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(90.)-298(doi:)-301.1(10.1016/j.immuni.2009.11.012)]TJ -8.3982 -1.2699 TD [(92.)-502.1(Xin)-315.3(A,)-319.6(Masson)-310.6(F,)-312.7(Liao)-320.5(Y,)-313.5(Preston)-314.8(S,)-311.8(Guan)-318.7(T,)-309.4(Gloury)-321.9(R,)-309.4(et)-317.6(al.)-312(A)-310.8(Molecular)]TJ 1.6781 -1.2699 TD 0.0279 Tc [(Thr)6.4(e)-2.1(s)6.4(h)-0.5(ol)5.8(d)-525.5(f)1.4(or)-522.8(Ef)69.4(fec)5.5(t)-2.7(o)6.3(r)-530.3(Cd8\(+\))-521.1(T)-529.8(Ce)5.5(ll)-523.4(Dif)69.4(f)1.4(ere)5.5(n)2(t)4.9(i)0.7(at)4.9(io)6.3(n)-527.2(C)3.6(ont)4.9(r)-1.2(o)6.3(l)-1.8(l)5.8(e)-2.1(d)-525.5(b)6.3(y)]TJ 0 -1.2624 TD 0 Tc [(Transcription)-322.4(Factors)-324.7(Blimp-1)-317.4(and)-316.2(T-Bet.)]TJ /F11 1 Tf 17.2273 0 TD [(Nat)-318.6(Immunol)]TJ /F6 1 Tf 5.7903 0 TD [(\(2016\))-315.8(17\(4\):422)]TJ /F8 1 Tf 6.705 0 TD ()Tj /F6 1 Tf -29.7226 -1.2699 TD [(32.)-305.6(doi:)-301.1(10.1038/ni.3410)]TJ -1.6781 -1.2624 TD [(93.)-502.1(Obar)-273.1(JJ,)-271.9(Jellison)-271.8(ER,)-276.6(Sheridan)-272.8(BS,)-273.1(Blair)-267.9(DA,)-270.9(Pham)-273.4(QM,)-274.5(Zickovich)-272.3(JM,)-268.2(et)-272.2(al.)]TJ 1.6781 -1.2699 TD 0.0232 Tc [(P)-4.4(a)-0.9(tho)-5.9(g)-2.6(en-Induced)-530.2(In)]TJ /F7 1 Tf 9.207 0 TD 0 Tc ()Tj /F6 1 Tf 0.5518 0 TD 0.0233 Tc [(ammatory)-531.6(Envir)-5.8(o)1.7(nme)-6.7(n)-2.6(t)-521.3(C)-1(ontr)-5.8(ols)-527.4(E)3.2(f)57.3(f)-3.2(ecto)-5.8(r)-519.8(and)]TJ -9.7589 -1.2624 TD 0 Tc [(Memory)-352.1(Cd8+)-358.2(T)-353.6(Cell)-348(Dif)63(ferentiation.)]TJ /F11 1 Tf 15.6852 0 TD [(J)-353.2(Immunol)]TJ /F6 1 Tf 4.6791 0 TD [(\(2011\))-353.6(187\(10\):4967)]TJ /F8 1 Tf 8.179 0 TD ()Tj /F6 1 Tf 0.5065 0 TD (78.)Tj -29.0498 -1.2699 TD [(doi:)-301.1(10.4049/jimmunol.1102335)]TJ -1.6781 -1.2699 TD [(94.)-502.1(Duckworth)-249.3(BC,)-243.8(Groom)-237.9(JR.)-244.4(Conversations)-253.5(That)-240.1(Count:)-241.3(Cellular)-251(Interactions)]TJ 1.6781 -1.2624 TD [(That)-353.5(Drive)-343.1(T)-346(Cell)-348(Fate.)]TJ /F11 1 Tf 9.9327 0 TD [(Immunol)-349.9(Rev)]TJ /F6 1 Tf 5.7903 0 TD [(\(2021\))-346(300\(1\):203)]TJ /F8 1 Tf 7.2114 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(19.)-350.9(doi:)-346.4(10.1111/)]TJ -23.4409 -1.2699 TD (imr.12945)Tj -1.6781 -1.2624 TD [(95.)-502.1(Oyler-Yaniv)-291.1(A,)-289.3(Oyler-Yaniv)-291.1(J,)-291.5(Whitlock)-290.3(BM,)-286.9(Liu)-284(Z,)-292.6(Germain)-286.9(RN,)-288.5(Huse)-290.9(M,)]TJ 1.6781 -1.2699 TD 0.0389 Tc [(e)-6.2(t)-543.5(a)-7.9(l)1.7(.)-544.4(A)-551.6(Tu)-8(na)-7.9(bl)-5.9(e)-542.9(D)-3.1(i)-3.5(f)57.8(fu)-8(s)-5.3(i)-3.5(on-)-7.7(C)-0.5(o)-5.4(n)-2.2(s)-5.3(u)-0.5(m)-3.3(p)-8(ti)-3.5(o)-5.4(n)-546.4(M)-5.9(e)1.4(c)-6.2(h)-4.6(ani)-3.5(s)-5.3(m)-547.5(o)-5.4(f)-547(C)-0.5(yt)-6.8(ok)-8.8(i)-3.5(n)-2.2(e)]TJ 0 -1.2624 TD 0 Tc [(P)-12.5(r)-14(o)-14(p)-9.1(a)-16.5(g)-10.7(a)-9(t)-15.5(i)-12.1(o)0(n)-531.3(E)-12.5(n)-10.8(a)-16.6(bl)-21(e)-14.9(s)-520.4(P)-12.5(l)-14.6(a)-9(s)-14(t)-7.9(i)-12.1(c)-14.9(i)-12.1(t)-15.5(y)-517.1(i)-12.1(n)-524.8(C)-16.8(e)0(l)-21.9(l)0(-)-23.4(T)-13.4(o-)-22.9(C)-9.2(e)-14.9(ll)-535.6(C)-9.2(o)-14(m)-11.9(m)-11.9(u)-9.1(n)-10.8(i)-12.1(c)-14.9(a)-16.6(t)-7.9(i)-12.1(o)-14(n)-524.8(i)-12.1(n)-517.3(t)-15.5(h)-13.3(e)]TJ 0 -1.2699 TD 0.0688 Tc [(Immu)6.7(ne)-565.9(S)7.7(y)-2.3(stem.)]TJ /F11 1 Tf 8.4814 0 TD 0.0671 Tc [(I)7(m)-6.1(munit)6.3(y)]TJ /F6 1 Tf 5.0646 0 TD 0.0656 Tc [(\(20)-7.2(17\))-566.5(46\()-7.2(4\):609)]TJ /F8 1 Tf 7.9447 0 TD 0 Tc ()Tj /F6 1 Tf 0.5821 0 TD 0.0664 Tc [(20.)-569.8(do)7(i)-6.2(:)-562.2(1)-6.4(0)1.1(.1016/)]TJ -22.0727 -1.2699 TD 0 Tc (j.immuni.2017.03.011)Tj -1.6781 -1.2624 TD 0.0211 Tc [(96.)-501.7(Duc)6.2(k)-3.9(wort)5.6(h)-521.3(B)-0.6(C,)-516.8(Lafouresse)-515.4(F,)-516.8(Wimmer)-514.4(V)0(C,)-516.8(Bro)7.1(o)-0.5(m)]TJ /F7 1 Tf 24.5143 0 TD 0 Tc ()Tj /F6 1 Tf 0.5518 0 TD 0.0208 Tc [(eld)-517.5(B)-0.9(J,)-517.1(Dalit)-516.3(L)0(,)]TJ -23.3275 -1.2699 TD 0 Tc [(A)-8.4(l)-14.6(e)-14.9(x)0(a)-17.2(n)-10.8(d)-16.7(r)0(e)-535.3(Y)-10(O)-9.4(,)-522.8(e)-14.9(t)-521.9(a)-9(l)0(.)-529.8(E)-12.5(f)49.1(f)-11.4(e)-14.9(c)0(t)-22.8(o)0(r)-526.9(a)-16.5(n)-10.8(d)-523.2(St)-23.7(em)-19.3(-)-8.8(L)-13.3(i)-12.1(k)-9.9(e)-521.3(M)-14.5(e)-14.9(m)0(o)-18.4(r)-14(y)-517.1(C)-16.8(el)-21.9(l)-521(F)-9.1(a)-16.5(t)-7.9(es)-535.3(A)-8.4(r)-14(e)]TJ 0 -1.2624 TD [(Imprinted)-475(in)-476.5(Distinct)-477(Lymph)-474(Node)-470.7(Niches)-479(Directed)-477.5(by)-470.7(Cxcr3)-474.3(Ligands.)]TJ /F11 1 Tf 0 -1.2699 TD [(Nat)-303.5(Immunol)]TJ /F6 1 Tf 5.7601 0 TD [(\(2021\))-300.7(22\(4\):434)]TJ /F8 1 Tf 6.6823 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(448.)-295.2(doi:)-301.1(10.1038/s41590-021-00878-5)]TJ 7.4999 0 0 7.4999 49.8331 274.9606 Tm [(97.)-502.1(Kurachi)-245.4(M,)-242.5(Kurachi)-245.4(J,)-238.6(Suenaga)-245.5(F,)-244.7(Tsukui)-241.5(T,)-241.4(Abe)-241.4(J,)-238.6(Ueha)-245.4(S,)-243.8(et)-242(al.)-236.4(Chemokine)]TJ 1.6781 -1.2699 TD [(Receptor)-375.2(Cxcr3)-376.1(Facilitates)-374.9(Cd8\(+\))-382.8(T)-368.7(Cell)-370.7(Dif)55.4(ferentiation)-374.1(Into)-372.5(Short-Lived)]TJ T* [(Ef)59.3(fector)-462.5(Cells)-452.7(Leading)-465.4(to)-452.8(Memory)-465.5(Degeneration.)]TJ /F11 1 Tf 20.7725 0 TD [(J)-459(Exp)-458.8(Med)]TJ /F6 1 Tf 4.9588 0 TD [(\(2011\))-459.4(208)]TJ -25.7313 -1.2624 TD (\(8\):1605)Tj /F8 1 Tf 3.3033 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(20.)-298(doi:)-301.1(10.1084/jem.20102101)]TJ -5.4955 -1.2699 TD [(98.)-502.1(Mempel)-223.5(TR,)-224.6(Henrickson)-224.6(SE,)-218.5(Von)-219.8(Andrian)-225.4(UH.)-220.6(T-Cell)-226.6(Priming)-220.2(by)-221.2(Dendritic)]TJ 1.6781 -1.2624 TD [(Cells)-293.9(in)-295.1(Lymph)-300.1(Nodes)-295.7(Occurs)-295.3(in)-295.1(Three)-297.1(Distinct)-295.6(Phases.)]TJ /F11 1 Tf 22.8211 0 TD (Nature)Tj /F6 1 Tf 3.0766 0 TD [(\(2004\))-293.1(427)]TJ -25.8976 -1.2699 TD (\(6970\):154)Tj /F8 1 Tf 4.2634 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(9.)-300.8(doi:)-308.6(10.1038/nature02238)]TJ -6.448 -1.2624 TD [(99.)-502.1(Eisenbarth)-455(SC.)-441.9(Dendritic)-447.8(Cell)-453.8(Subsets)-444.9(in)-446.3(T)-444.3(Cell)-446.3(Programming:)-450.2(Location)]TJ 1.6781 -1.2699 TD [(Dictates)-455.3(Function.)]TJ /F11 1 Tf 7.9522 0 TD [(Nat)-454.7(Rev)-449.7(Immunol)]TJ /F6 1 Tf 7.9371 0 TD [(\(2019\))-451.9(19\(2\):89)]TJ /F8 1 Tf 6.3572 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(103.)-454(doi:)-452.2(10.1038/)]TJ -22.753 -1.2699 TD (s41577-018-0088-1)Tj -2.2753 -1.2624 TD [(100.)-499.3(Eickhof)55.6(f)-344(S)0(,)-357.2(Brewitz)-345.8(A,)-349.8(Gerner)-358.3(MY,)-350.7(Klauschen)-349.1(F,)-350.5(Komander)-355(K,)-348.1(Hemmi)-356.7(H,)]TJ 2.1544 -1.2699 TD [(e)-14.9(t)-514.4(a)-9(l)-14.6(.)-515.2(R)-13.4(ob)-20.5(u)-9.1(s)0(t)-528.3(A)-8.4(n)-10.8(t)-7.9(i)-12.1(-)-8.8(Vi)-18.1(ra)-22.9(l)-513.5(I)-14.7(mm)-16.3(u)-9.1(n)-10.8(i)-12.1(t)-7.9(y)-517.1(R)-13.4(eq)-18.9(u)-9.1(i)-12.1(re)-21.3(s)-512.9(M)-14.5(u)-9.1(l)0(t)-14.9(i)-12.1(p)-9.1(l)-14.6(e)-513.8(D)-11.8(i)-12.1(s)0(t)-14.3(i)-12.1(n)-10.8(c)0(t)-529.3(T)-519.9(C)-9.2(e)0(l)-21.9(l)0(-)]TJ 0 -1.2624 TD 0.0147 Tc [(D)-4.7(e)-0.2(ndri)-5(tic)-514.2(C)-2.1(ell)-513.9(I)0(nteractions.)]TJ /F11 1 Tf 12.3139 0 TD 0.0167 Tc (Cell)Tj /F6 1 Tf 2.0712 0 TD 0.0126 Tc [(\()-7.2(201)-7.3(5\))-521.3(162)-7.3(\(6\))-7.2(:132)-7.3(2)]TJ /F8 1 Tf 8.111 0 TD 0 Tc ()Tj /F6 1 Tf 0.5216 0 TD 0.0129 Tc [(3)-7(7)0.6(.)-517.5(d)-3.8(oi:)-517.5(1)-7(0.10)-7(16/)]TJ -23.0176 -1.2699 TD 0 Tc (j.cell.2015.08.004)Tj -2.1544 -1.2624 TD 0.0207 Tc [(101.)-502.1(Hor)-522.4(J)2.5(L,)-517.2(Whitney)-519.1(P)0.6(G,)-524.8(Zai)-6.5(d)-517.6(A,)-517.2(Bro)6.7(o)-0.9(k)-4.3(s)-514.8(AG,)-524.8(H)2.1(eath)-521.7(W)6(R)-0.3(,)-524.8(M)-1.4(uell)6.1(er)-522.4(SN.)]TJ 2.2375 -1.2699 TD 0.0313 Tc [(Spa)-7.9(t)0.7(iote)-6.2(mpor)-5.3(all)-5.9(y)-531.2(Dist)-6.9(inc)-6.2(t)-536(Inte)-6.2(rac)-6.2(t)0.7(ions)-534.5(W)-6.1(i)-3.5(th)-533.8(Dendr)-5.3(i)-3.5(tic)-535.4(C)-0.6(el)-5.9(l)-535.1(S)0.4(ub)-5.4(se)-6.3(ts)]TJ T* 0 Tc [(Facilitates)-367.3(Cd4+)-358.2(and)-361.5(Cd8+)-365.8(T)-361.1(Cell)-355.6(Activation)-364.9(to)-362.1(Localized)-366.1(Viral)-358(Infection.)]TJ /F11 1 Tf 0 -1.2624 TD (Immunity)Tj /F6 1 Tf 4.2709 0 TD [(\(2015\))-300.7(43\(3\):554)]TJ /F8 1 Tf 6.6823 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(65.)-298(doi:)-301.1(10.1016/j.immuni.2015.07.020)]TJ -13.7047 -1.2699 TD [(102.)-499.3(Mackley)-269.8(EC,)-257.2(Houston)-269.9(S,)-258.9(Marriott)-267.3(CL,)-258(Halford)-264.5(EE,)-268.1(Lucas)-264.3(B,)-264.8(Cerovic)-263.5(V,)-264.2(et)-257.1(al.)]TJ 2.1544 -1.2624 TD 0.0237 Tc [(C)-8.2(c)1.3(r)-5.4(7)-3.8(-Dep)-8.1(en)-9.8(de)-6.3(nt)-528.5(Tr)-5.4(af)]TJ /F7 1 Tf 9.3204 0 TD 0 Tc ()Tj /F6 1 Tf 0.5594 0 TD 0.0267 Tc [(cking)-528.2(o)5.1(f)-528.9(R)-1.8(o)5.1(r)-2.4(gamma\(+\))-522.3(I)-3.1(lcs)-524(C)-5.2(r)5.2(e)-3.3(ates)-531.5(a)-519(U)-0.2(n)-6.8(i)7(que)]TJ -9.8798 -1.2699 TD 0 Tc [(Microenvironment)-308.1(Within)-305.3(Mucosal)-301.7(Draining)-310.5(Lymph)-300.1(Nodes.)]TJ /F11 1 Tf 24.8394 0 TD [(Nat)-303.5(Commun)]TJ /F6 1 Tf -24.8394 -1.2624 TD [(\(2015\))-300.7(6:5862.)-306(doi:)-301.1(10.1038/ncomms6862)]TJ 32.6177 84.8666 TD [(103.)-499.3(Withers)-347.8(DR,)-343.9(Gaspal)-345.4(FM,)-342.4(Mackley)-345.4(EC,)-347.9(Marriott)-342.9(CL,)-341.2(Ross)-342.6(EA,)-347.2(Desanti)-345(GE,)]TJ 2.1544 -1.2699 TD [(et)-219.3(al.)-221.3(Cutting)-219(Edge:)-222.2(Lymphoid)-222(Tissue)-221.1(Inducer)-223.6(Cells)-218.3(Maintain)-222.4(Memory)-223.6(Cd4)-219.7(T)]TJ 0 -1.2624 TD [(Cells)-248.6(Within)-252.3(Secondary)-256.7(Lymphoid)-252.3(Tissue.)]TJ /F11 1 Tf 17.0686 0 TD [(J)-254.9(Immunol)]TJ /F6 1 Tf 4.4826 0 TD [(\(2012\))-247.8(189\(5\):2094)]TJ /F8 1 Tf 7.5894 0 TD ()Tj /F6 1 Tf 0.514 0 TD (8.)Tj -29.6545 -1.2699 TD [(doi:)-301.1(10.4049/jimmunol.1201639)]TJ -2.1544 -1.2624 TD [(104.)-499.3(Li)-433.6(L,)-430.2(Wu)-432(J,)-427.6(Abdi)-436.8(R,)-430.4(Jewell)-428.1(CM,)-433.1(Bromberg)-432.6(JS.)-435.8(Lymph)-428.6(Node)-432.9(Fibroblastic)]TJ 2.1544 -1.2699 TD [(Reticular)-230.8(Cells)-233.5(Steer)-226.1(Immune)-232.2(Responses.)]TJ /F11 1 Tf 16.3882 0 TD [(Trends)-232(Immunol)]TJ /F6 1 Tf 6.841 0 TD [(\(2021\))-225.1(42\(8\):723)]TJ /F8 1 Tf 6.6067 0 TD ()Tj /F6 1 Tf -29.836 -1.2699 TD [(34.)-305.6(doi:)-301.1(10.1016/j.it.2021.06.006)]TJ -2.1544 -1.2624 TD [(105.)-499.3(Brown)-222.6(FD,)-218.7(Sen)-215.3(DR,)-215.4(LaFleur)-220(MW,)-219.4(Godec)-221.7(J,)-215.9(Lukacs-Kornek)-224.8(V,)-218.8(Schildberg)-216.4(FA,)]TJ 2.1544 -1.2699 TD [(et)-347.8(al.)-342.3(Fibroblastic)-346.2(Reticular)-351.7(Cells)-346.8(Enhance)-350.7(T)-338.5(Cell)-348(Metabolism)-346.1(and)-346.4(Survival)]TJ /F11 1 Tf 0 -1.2624 TD 0.0461 Tc (Via)Tj /F6 1 Tf 2.1014 0 TD 0.0434 Tc [(Ep)4(igenet)5.2(ic)-546(Remod)4(e)-1.7(ling.)]TJ /F11 1 Tf 11.1497 0 TD 0.0432 Tc [(Nat)-546.8(I)5.8(mmunol)]TJ /F6 1 Tf 6.6672 0 TD 0.0428 Tc [(\(2019)-7.3(\))-536.4(2)-7.3(0\(12\):1668)]TJ /F8 1 Tf 8.6174 0 TD 0 Tc ()Tj /F6 1 Tf 0.5518 0 TD 0.0426 Tc (80.)Tj -29.0876 -1.2699 TD 0 Tc [(doi:)-301.1(10.1038/s41590-019-0515-x)]TJ -2.1544 -1.2624 TD [(106.)-499.3(Knoblich)-274.3(K,)-272.5(Cruz)-281.5(Migoni)-270.8(S,)-274(Siew)-272.9(SM,)-273.4(Jinks)-276.6(E,)-278.3(Kaul)-273.8(B,)-272.4(Jef)61.4(fery)-277.6(HC,)-270.9(et)-272.2(al.)-274.2(The)]TJ 2.1544 -1.2699 TD [(H)-11(u)-9.1(m)-11.9(a)-9(n)-524.8(L)-13.3(y)-10.7(m)-11.9(p)-9.1(h)-519.7(N)-9.4(o)-14(d)-9.1(e)-521.3(Mi)-19.1(c)-14.9(r)0(o)-20.4(e)0(n)-18.1(v)-10.7(i)-12.1(r)-14(on)-17.3(m)-11.9(e)-14.9(n)-10.8(t)-514.4(U)-11.8(n)-10.8(i)-12.1(l)-14.6(a)-9(t)-7.9(e)-14.9(r)0(a)-15.4(l)-14.6(ly)-531.7(Re)-20.7(g)-10.7(u)-9.1(l)-14.6(a)-9(t)-7.9(e)-14.9(s)-520.4(T)0(-)-22.2(C)-9.2(el)-21.9(l)]TJ T* 0.0509 Tc [(Ac)5.8(tiva)4.1(tio)6.6(n)-549.5(and)-547.9(D)1.3(if)50.9(f)13.1(e)-1.8(r)6.7(e)-1.8(ntia)4.1(t)5.2(i)1(on.)]TJ /F11 1 Tf 14.8159 0 TD 0.0466 Tc [(P)-6.1(L)-4.5(oS)-553.7(Bi)-8.4(ol)]TJ /F6 1 Tf 5.0571 0 TD 0.0501 Tc [(\(2018\))-551.8(1)7.5(6\(9\):e2005046.)]TJ -19.873 -1.2624 TD 0 Tc [(doi:)-301.1(10.1371/journal.pbio.2005046)]TJ -2.1544 -1.2699 TD [(107.)-499.3(Gerard)-464.1(A,)-463.2(Khan)-463.1(O,)-456.6(Beemiller)-466.1(P,)-459.7(Oswald)-467.5(E,)-459.7(Hu)-458.6(J,)-465.4(Matloubian)-462.8(M,)-461.7(et)-461.2(al.)]TJ 2.1544 -1.2624 TD [(Secondary)-362.5(T)-353.6(Cell-T)-355.1(Cell)-355.6(Synaptic)-354.9(Interactions)-356.6(Drive)-358.2(the)-353.5(Dif)63(ferentiation)-359(of)]TJ 0 -1.2699 TD [(Protective)-358(Cd8+)-358.2(T)-361.1(Cells.)]TJ /F11 1 Tf 10.4241 0 TD [(Nat)-356.4(Immunol)]TJ /F6 1 Tf 5.8659 0 TD [(\(2013\))-361.2(14\(4\):356)]TJ /F8 1 Tf 6.7428 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(63.)-350.9(doi:)-361.5(10.1038/)]TJ -23.5468 -1.2624 TD (ni.2547)Tj -2.1544 -1.2699 TD [(108.)-499.3(Krummel)-362.8(MF,)-365(Mahale)-362.4(JN,)-361.3(Uhl)-357.1(LFK,)-363(Hardison)-358.6(EA,)-362.3(Mujal)-364.1(AM,)-356.8(Mazet)-363.5(JM,)]TJ 2.1544 -1.2699 TD 0.0236 Tc [(et)-521(al.)-521.9(P)-4(aracrin)5.2(e)-520.4(Costimu)6.9(l)1.5(ation)-523.9(o)2(f)-524.5(I)]TJ 15.5567 0 TD [(f)4.7(n)-2.3(-G)5.9(amma)-522.1(Sig)5.4(n)-2.3(aling)-523.8(b)2(y)-523.8(I)1.3(n)5.2(t)0.5(egrin)5.2(s)]TJ -15.5567 -1.2624 TD 0 Tc [(Modulates)-454.8(Cd8)-454(T)-451.8(Cell)-453.8(Dif)63(ferentiation.)]TJ /F11 1 Tf 16.3731 0 TD [(Proc)-455.8(Natl)-450(Acad)-451.8(Sci)-454.2(U.S.A.)]TJ /F6 1 Tf 11.369 0 TD (\(2018\))Tj -27.7421 -1.2699 TD (115\(45\):11585)Tj /F8 1 Tf 5.6996 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(90.)-305.6(doi:)-301.1(10.1073/pnas.1804556115)]TJ -8.3604 -1.2624 TD [(109.)-499.3(Fuhrmann)-481.1(F,)-471.5(Lischke)-477.7(T,)-468.2(Gross)-474.2(F,)-479(Scheel)-473.7(T,)-475.7(Bauer)-469.3(L,)-475.6(Kalim)-477.7(KW,)-468.6(et)-476.3(al.)]TJ 2.1544 -1.2699 TD [(Adequate)-500.7(Immune)-496.7(Response)-498.1(Ensured)-500.1(by)-493.4(Binary)-494(Il-2)-496.5(and)-490.1(Graded)-504.6(Cd25)]TJ 0 -1.2624 TD [(Expression)-267.1(in)-257.3(a)-258.4(Murine)-264.4(Transfer)-260(Model.)]TJ /F11 1 Tf 16.3353 0 TD (Elife)Tj /F6 1 Tf 1.9881 0 TD [(\(2016\))-262.9(5:e20616.)-257.6(doi:)-263.3(10.7554/)]TJ -18.3234 -1.2699 TD (eLife.20616)Tj -2.1544 -1.2699 TD [(110.)-499.3(Tkach)-219.2(KE,)-224.6(Barik)-217.9(D,)-224.7(Voisinne)-215.7(G,)-223(Malandro)-223.5(N,)-214.7(Hathorn)-223.6(MM,)-219.3(Cotari)-217.4(JW,)-223(et)-219.3(al.)]TJ 2.1544 -1.2624 TD [(T)-459.4(Cells)-460.2(Translate)-455.2(Individual,)-460.3(Quantal)-462.8(Activation)-463.2(Into)-455.7(Collective,)-461.5(Analog)]TJ 0 -1.2699 TD [(Cytokine)-331.4(Responses)]TJ /F11 1 Tf 8.3831 0 TD (Via)Tj /F6 1 Tf 1.7462 0 TD [(Time-Integrated)-333.7(Feedbacks.)]TJ /F11 1 Tf 11.505 0 TD (Elife)Tj /F6 1 Tf 2.0561 0 TD [(\(2014\))-330.9(3:e01944.)]TJ -23.6904 -1.2624 TD [(doi:)-301.1(10.7554/eLife.01944)]TJ 7.4999 0 0 7.4999 306.1417 417.4298 Tm [(111.)-499.3(Amado)-294.4(IF,)-297.2(Berges)-294.1(J,)-291.5(Luther)-291.6(RJ,)-297.4(Mailhe)-290(MP,)-292.8(Garcia)-295.8(S,)-289.1(Bandeira)-297.1(A,)-296.9(et)-287.4(al.)-296.9(Il-2)]TJ 2.1544 -1.2624 TD [(Coordinates)-461.6(Il-2-Producing)-468.8(and)-459.8(Regulatory)-465.9(T)-459.4(Cell)-453.8(Interplay.)]TJ /F11 1 Tf 25.8523 0 TD [(J)-459(Exp)-458.8(Med)]TJ /F6 1 Tf -25.8523 -1.2699 TD [(\(2013\))-300.7(210\(12\):2707)]TJ /F8 1 Tf 8.1261 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(20.)-305.6(doi:)-301.1(10.1084/jem.20122759)]TJ -10.7869 -1.2699 TD [(112.)-499.3(Feinerman)-379.6(O,)-373.4(Jentsch)-373.5(G,)-374.2(Tkach)-370.3(KE,)-375.7(Coward)-368.5(JW,)-374.2(Hathorn)-374.8(MM,)-378(Sneddon)]TJ 2.1544 -1.2624 TD [(MW,)-506.6(et)-499(al)-8.4(.)-500.1(Single-Cel)-12.9(l)-498.3(Quanti)]TJ /F7 1 Tf 12.843 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(ca)-8.7(tion)-498.4(of)-509.2(Il-2)-504(Response)-505.6(by)-500.9(Ef)59.3(fect)-11.2(or)-496.7(and)]TJ -13.3721 -1.2699 TD [(Regulatory)-465.9(T)-467(Cells)-467.8(Reveals)-461.7(Critical)-471.7(Plasticity)-463.3(in)-468.9(Immune)-466.5(Response.)]TJ /F11 1 Tf 28.7701 0 TD (Mol)Tj -28.7701 -1.2624 TD [(Syst)-299.3(Biol)]TJ /F6 1 Tf 3.6813 0 TD [(\(2010\))-308.2(6:437.)-301.2(doi:)-301.1(10.1038/msb.2010.90)]TJ -5.8357 -1.2699 TD [(113.)-499.3(Zenke)-477.9(S,)-478.1(Palm)-478.9(MM,)-476.3(Braun)-480.4(J,)-472.9(Gavrilov)-480.6(A,)-478.3(Meiser)-477.4(P,)-474.8(Bottcher)-478.9(JP,)-477.8(et)-476.3(al.)]TJ 2.1544 -1.2624 TD [(Quorum)-226.3(Regulation)]TJ /F11 1 Tf 8.2017 0 TD (Via)Tj /F6 1 Tf 1.6403 0 TD [(Nested)-221.3(Antagonistic)-223.3(Feedback)-224.3(Circuits)-221.8(Mediated)-220.1(by)]TJ -9.842 -1.2699 TD [(the)-406.4(Receptors)-411.8(Cd28)-405.9(and)-406.9(Ctla-4)-409.6(Confers)-405.7(Robustness)-413.3(to)-407.5(T)-406.5(Cell)-400.9(Population)]TJ T* 0.1017 Tc (Dynamics.)Tj /F11 1 Tf 5.745 0 TD 0.1051 Tc [(Im)9.2(mun)8.7(i)4.7(ty)]TJ /F6 1 Tf 5.3746 0 TD 0.1028 Tc [(\(202)7.3(0\))-597.4(52\()7.4(2\):313)]TJ /F8 1 Tf 8.4965 0 TD 0 Tc ()Tj /F6 1 Tf 0.6123 0 TD 0.1029 Tc [(27)7.4(.e)4.9(7.)-601.3(do)5.7(i:)-601.3(1)7.4(0)-0.2(.1016)7.4(/)]TJ -20.2283 -1.2624 TD 0 Tc (j.immuni.2020.01.018)Tj -2.1544 -1.2699 TD [(114.)-499.3(Polonsky)-266.7(M,)-265.2(Rimer)-262.8(J,)-268.8(Kern-Perets)-269.3(A,)-266.7(Zaretsky)-265.8(I,)-265.4(Miller)-258.5(S,)-266.4(Bornstein)-271.4(C,)-259.8(et)-264.7(al.)]TJ 2.1544 -1.2624 TD [(Induction)-458.8(of)-456.2(Cd4)-454(T)-459.4(Cell)-453.8(Memory)-457.9(by)-455.6(Local)-451.2(Cellular)-462.7(Collectivity.)]TJ /F11 1 Tf 27.5455 0 TD (Science)Tj /F6 1 Tf -27.5455 -1.2699 TD [(\(2018\))-300.7(360\(6394\):eaaj1853.)-308.4(doi:)-301.1(10.1126/science.aaj1853)]TJ -2.1544 -1.2624 TD [(115.)-499.3(Petkau)-214.5(G,)-207.9(Mitchell)-212.5(TJ,)-214.2(Chakraborty)-215.5(K,)-204.5(Bell)-216.9(SE,)-210.9(D)-208.3(Angeli)-207.5(V,)-211.3(Matheson)-211.7(L,)-211(et)-211.8(al.)]TJ 2.1544 -1.2699 TD [(The)-215.4(Timing)-207.1(of)-214.4(Dif)63(ferentiation)-215.4(and)-210.4(Potency)-214.1(of)-206.8(Cd8)-212.1(Ef)59.3(fector)-213.1(Function)-209.8(Is)-210.1(Set)-212.4(by)]TJ T* [(Rna)-222.2(Binding)-215.9(Proteins.)]TJ /F11 1 Tf 8.9425 0 TD [(Nat)-220.4(Commun)]TJ /F6 1 Tf 5.6391 0 TD [(\(2022\))-225.1(13\(1\):2274.)-219.2(doi:)-217.9(10.1038/s41467-)]TJ -14.5816 -1.2624 TD (022-29979-x)Tj -2.1544 -1.2699 TD [(116.)-499.3(Voisinne)-427.3(G,)-419.5(Nixon)-417.4(BG,)-426.1(Melbinger)-422.8(A,)-417.8(Gasteiger)-424.9(G,)-419.5(Vergassola)-422.3(M,)-423.9(Altan-)]TJ 2.1544 -1.2624 TD [(Bonnet)-261.6(G.)-260.8(T)-262.9(Cells)-256.1(Integrate)-263.5(Local)-262.2(and)-263.3(Global)-257.7(Cues)-258.8(to)-263.8(Discriminate)-258.9(Between)]TJ 0 -1.2699 TD [(Structurally)-330.4(Similar)-331.4(Antigens.)]TJ /F11 1 Tf 12.2836 0 TD [(Cell)-323.7(Rep)]TJ /F6 1 Tf 3.6208 0 TD [(\(2015\))-323.4(11\(8\):1208)]TJ /F8 1 Tf 7.1888 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(19.)-320.7(doi:)-331.3(10.1016/)]TJ -23.6072 -1.2624 TD (j.celrep.2015.04.051)Tj -2.1544 -1.2699 TD [(117.)-499.3(Au-Yeung)-263.3(BB,)-263.9(Smith)-265.1(GA,)-261.7(Mueller)-270.3(JL,)-259.4(Heyn)-266.6(CS,)-260.5(Jaszczak)-270.9(RG,)-259.1(Weiss)-266.1(A,)-259.1(et)-264.7(al.)]TJ 2.1544 -1.2699 TD [(Il-2)-398.2(Modulates)-394.4(the)-391.3(Tcr)-397.5(Signaling)-393.8(Threshold)-400.1(for)-394.6(Cd8)-393.5(But)-394.1(Not)-394.1(Cd4)-393.5(T)-391.4(Cell)]TJ 0 -1.2624 TD [(Pr)-11.3(olife)-14(rati)-12.8(on)-508.6(on)-508.6(a)-507.9(Sing)-11.6(le-C)-9.7(ell)-512.7(Leve)-15.9(l.)]TJ /F11 1 Tf 15.7533 0 TD [(J)-504.4(Imm)-9.9(uno)-12.1(l)]TJ /F6 1 Tf 5.0042 0 TD [(\(2)-9.5(017\))-510.4(19)-9.6(8\(6\))-11.4(:24)-10.8(45)]TJ /F8 1 Tf 7.8918 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(56)-9.6(.)]TJ -29.1632 -1.2699 TD [(doi:)-301.1(10.4049/jimmunol.1601453)]TJ -2.1544 -1.2624 TD [(118.)-499.3(B)46.3(r)46.5(z)45.6(o)46.5(s)46.5(t)45(e)45.6(k)-327.4(J)42.3(,)-326.3(G)42.8(a)51.5(u)43.8(t)45(a)43.9(m)-329.4(N)51.1(,)-333.8(Z)48.7(h)47.2(a)43.9(o)-331.5(X)47.8(,)-326.3(C)43.7(h)47.2(e)45.6(n)-328.3(E)48(W)45.8(,)-333.8(M)45.9(e)45.6(h)47.2(t)45(a)-326.5(M)45.9(,)-326.3(T)39.5(u)51.3(n)42.1(g)-328.2(D)48.7(W)45.8(H)41.9(,)-326.3(e)45.6(t)-333(a)51.5(l)45.9(.)-333.8(T)-323.3(C)43.7(e)45.6(l)45.9(l)]TJ 2.1544 -1.2699 TD -0.0455 Tc [(Receptor)-399.6(a)-1.6(nd)-402.4(Cyt)7.1(o)0.9(kine)-400.5(Signal)-400.2(Integra)6(t)]TJ 14.3246 0 TD -0.0453 Tc [(io)8.7(n)-403.8(i)-4.5(n)-403.8(C)6(d8\(+\))-405.3(T)-398.9(Cells)-399.4(Is)-407(Med)6(i)-4.5(a)6.2(t)-0.3(ed)-402.2(by)-403.7(the)]TJ -14.3246 -1.2624 TD -0.0469 Tc [(Protein)-246.7(T)0.2(hemi)-6.1(s.)]TJ /F11 1 Tf 6.002 0 TD -0.0481 Tc [(Nat)-245(I)-2.3(mmun)-8.4(o)4.1(l)]TJ /F6 1 Tf 5.1705 0 TD -0.0406 Tc [(\()7.6(2)7.5(02)7.5(0)7.5(\))-234.3(21)7.5(\()7.6(2)7.5(\):)11.1(18)7.5(6)]TJ /F8 1 Tf 5.9264 0 TD 0 Tc ()Tj /F6 1 Tf 0.4611 0 TD -0.0473 Tc [(9)-6.7(8)0.8(.)-245.1(d)4(oi)-6.5(:)-237.5(1)-6.7(0.1038/)-5(s415)-6.7(90-019-05)-6.7(70-3)]TJ -19.7143 -1.2699 TD 0.0207 Tc [(11)8.4(9.)-502.1(R)7.3(o)-0.9(ss)-484.6(S)4.9(H)2.1(,)-487(C)3.9(a)4.1(n)2.3(tr)6.7(el)6.1(l)-485.2(D)1.3(A)4.7(.)-487(Signa)4.2(l)6.1(ing)-488.9(a)4.2(nd)-487.3(F)4(u)4(n)2.3(ct)5.2(ion)-481.5(o)-0.9(f)-482(I)-1.6(nt)5.2(er)6.7(le)5.8(uki)8.6(n)-5.2(-)4.3(2)-483(in)-481.5(T)]TJ 2.2299 -1.2699 TD 0 Tc (Lymphocytes.)Tj /F11 1 Tf 5.8054 0 TD [(Annu)-283.3(Rev)-275.8(Immunol)]TJ /F6 1 Tf 8.179 0 TD [(\(2018\))-278(36:411)]TJ /F8 1 Tf 5.4955 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(33.)-282.9(doi:)-278.4(10.1146/annurev-)]TJ -19.9864 -1.2624 TD (immunol-042617-053352)Tj -2.2299 -1.2699 TD [(120.)-499.3(Shyer)-219.7(JA,)-216.8(Flavell)-215.9(RA,)-212(Bailis)-219.6(W.)-212.4(Metabolic)-221.7(Signaling)-219.9(in)-211.9(T)-217.5(Cells.)]TJ /F11 1 Tf 26.646 0 TD [(Cell)-217.9(Res)]TJ /F6 1 Tf 3.258 0 TD (\(2020\))Tj -27.7496 -1.2624 TD (30\(8\):649)Tj /F8 1 Tf 3.7796 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(59.)-298(doi:)-301.1(10.1038/s41422-020-0379-5)]TJ -6.448 -1.2699 TD 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[(130.)-499.3(Su)-448.2(Y,)-449.6(Chen)-448.8(D,)-451.4(Yuan)-447.1(D,)-451.4(Lausted)-447.6(C,)-448.8(Choi)-449.2(J,)-450.2(Dai)-448.7(CL,)-447(et)-446.1(al.)-455.6(Multi-Omics)]TJ 2.1544 -1.2699 TD [(Resolves)-284.1(a)-288.7(Sharp)-280.3(Disease-State)-290.9(Shift)-279.7(Between)-284.9(Mild)-284.7(and)-285.9(Moderate)-287.3(Covid-19.)]TJ /F11 1 Tf 0 -1.2624 TD (Cell)Tj /F6 1 Tf 1.7991 0 TD [(\(2020\))-308.2(183\(6\):1479)]TJ /F8 1 Tf 7.6499 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(95.e20.)-301(doi:)-301.1(10.1016/j.cell.2020.10.037)]TJ -12.1098 -1.2699 TD [(131.)-499.3(Makedonas)-279(G,)-275.9(Hutnick)-279.9(N,)-275.1(Haney)-275.6(D,)-277.6(Amick)-276.5(AC,)-275.9(Gardner)-278.4(J,)-276.4(Cosma)-277.3(G,)-275.9(et)-272.2(al.)]TJ 2.1544 -1.2699 TD [(Perforin)-209.4(and)-210.4(Il-2)-201.6(Upregulation)-213.6(De)]TJ /F7 1 Tf 13.4855 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(ne)-207.1(Qualitative)-207.4(Dif)63(ferences)-207.8(Among)-207(Highly)]TJ -14.0222 -1.2624 TD [(Functional)-422.3(Virus-Speci)]TJ /F7 1 Tf 9.3582 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(c)-415.5(Human)-422.3(Cd8)-416.2(T)-414(Cells.)]TJ /F11 1 Tf 9.9932 0 TD [(PLoS)-417.5(Pathog)]TJ /F6 1 Tf 5.5862 0 TD [(\(2010\))-414.1(6\(3\):)]TJ -25.4668 -1.2699 TD [(e1000798.)-306.5(doi:)-301.1(10.1371/journal.ppat.1000798)]TJ 7.4999 0 0 7.4999 45.3543 360.4535 Tm [(132.)-499.3(Sallusto)-424(F,)-418.5(Lenig)-424.6(D,)-421.2(Forster)-420.4(R,)-415.3(Lipp)-421.6(M,)-423.9(Lanzavecchia)-426.2(A.)-417.8(Two)-416.3(Subsets)-422.2(of)]TJ 2.1544 -1.2699 TD [(Memory)-488.2(T)-489.6(Lymphocytes)-489.8(With)-486.4(Distinct)-492.2(Homing)-486.3(Potentials)-488.1(and)-490(Ef)59.3(fector)]TJ 0 -1.2624 TD (Functions.)Tj /F11 1 Tf 4.4901 0 TD (Nature)Tj /F6 1 Tf 3.0841 0 TD [(\(1999\))-300.7(401\(6754\):708)]TJ /F8 1 Tf 8.5948 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(12.)-298(doi:)-308.6(10.1038/44385)]TJ -18.8374 -1.2699 TD [(133.)-499.3(Nicolet)-427.9(BP,)-420.9(Guislain)-424.4(A,)-417.8(van)-423.5(Alphen)-426.3(FPJ,)-419(Gomez-Eerland)-431.6(R,)-422.8(Schumacher)]TJ 2.1544 -1.2699 TD [(TNM,)-393.8(van)-393.3(den)-397.7(Biggelaar)-396.2(M,)-393.7(et)-385.6(al.)-395.2(Cd29)-390.7(Identi)]TJ /F7 1 Tf 19.4195 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(es)-391.7(Ifn-Gamma-Producing)]TJ -19.9486 -1.2624 TD [(Human)-384.5(Cd8\(+\))-382.8(T)-383.8(Cells)-384.6(With)-380.6(an)-382.6(Increased)-380.7(Cytotoxic)-386.2(Potential.)]TJ /F11 1 Tf 26.4797 0 TD [(Proc)-380.2(Natl)]TJ -26.4797 -1.2699 TD [(Acad)-300.6(Sci)-303(U.S.A.)]TJ /F6 1 Tf 6.5235 0 TD [(\(2020\))-308.2(117\(12\):6686)]TJ /F8 1 Tf 8.1261 0 TD ()Tj /F6 1 Tf 0.514 0 TD [(96.)-298(doi:)-301.1(10.1073/pnas.1913940117)]TJ -17.318 -1.2624 TD [(134.)-499.3(Low)-242.2(JS,)-246.8(Farsakoglu)-241.8(Y,)-245.5(Amezcua)-249.4(Vesely)-241.2(MC,)-244.2(Se)]TJ /F7 1 Tf 20.7121 0 TD ()Tj /F6 1 Tf 0.5291 0 TD [(k)-244.2(E)0(,)-240.5(Kelly)-250.4(JB,)-237.6(Harman)-247.1(CCD,)]TJ -19.0869 -1.2699 TD [(et)-476.3(al.)-478.3(Tissue-Resident)-485.7(Memory)-480.6(T)-474.5(Cell)-476.5(Reactivation)-484.4(by)-478.2(Diverse)-477.7(Antigen-)]TJ 0 -1.2624 TD [(Presenting)-349.2(Cells)-339.3(Imparts)-345.2(Distinct)-341(Functional)-346.7(Responses.)]TJ /F11 1 Tf 23.1386 0 TD [(J)-345.6(Exp)-337.9(Med)]TJ /F6 1 Tf 4.6111 0 TD (\(2020\))Tj -27.7496 -1.2699 TD [(217\(8\):e20192291.)-310.9(doi:)-301.1(10.1084/jem.20192291)]TJ -2.1544 -1.2699 TD [(135.)-499.3(Sanchez)-426(A,)-425.4(Golding)-421.6(I.)-424.1(Genetic)-418.2(Determinants)-427.2(and)-422(Cellular)-424.9(Constraints)-426(in)]TJ 2.1544 -1.2624 TD [(Noisy)-453.2(Gene)-458.9(Expression.)]TJ /F11 1 Tf 10.3485 0 TD (Science)Tj /F6 1 Tf 3.258 0 TD [(\(2013\))-451.9(342\(6163\):1188)]TJ /F8 1 Tf 9.2373 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(93.)-456.8(doi:)-452.2(10.1126/)]TJ -23.3502 -1.2699 TD (science.1242975)Tj -2.1544 -1.2624 TD [(136.)-499.3(F)21.1(e)30.5(i)25.7(n)27(e)22.9(r)23.8(m)25.8(a)28.8(n)-305.6(O)20.9(,)-311.1(V)31.8(e)22.9(i)25.7(g)27.1(a)-311.4(J)27.2(,)-311.1(D)26(o)31.3(r)23.8(f)26.4(m)25.9(a)28.8(n)-313.2(J)27.2(R)24.4(,)-311.1(G)27.7(e)30.5(r)23.8(m)25.8(a)28.8(i)25.7(n)-313.2(R)24.4(N)28.4(,)-311.1(A)29.4(l)23.2(t)29.9(a)28.8(n)19.4(-)29(B)23.6(o)31.3(n)27(n)27(e)22.9(t)-310.3(G)27.7(.)-311.1(V)24.2(a)28.8(r)23.8(i)25.7(a)28.8(b)23.8(i)25.7(l)30.8(i)25.7(t)29.9(y)]TJ 2.1544 -1.2699 TD -0.024 Tc [(and)-335.5(R)0.4(ob)7.3(us)7.4(tne)6.5(s)-0.2(s)-340.3(i)1.7(n)-337.2(T)-339.8(Cel)6.8(l)-340.9(A)5.4(c)-1.1(ti)9.2(vat)5.9(i)1.7(on)-337.2(From)]TJ 16.8267 0 TD [(Re)6.5(gul)6.8(a)-2.8(t)5.9(e)-1.1(d)-335.5(H)2.8(et)5.9(er)7.4(ogenei)9.2(ty)-337(in)-337.2(Pro)7.3(t)-1.7(e)6.5(i)1.7(n)]TJ -16.8267 -1.2624 TD -0.0248 Tc [(Leve)5.7(ls.)]TJ /F11 1 Tf 2.7742 0 TD -0.0265 Tc (Science)Tj /F6 1 Tf 2.9103 0 TD -0.0252 Tc [(\(2008\))-294.5(321\(589)7.8(2\):1)7.8(0)0.2(81)]TJ /F8 1 Tf 8.5494 0 TD 0 Tc ()Tj /F6 1 Tf 0.4838 0 TD -0.0259 Tc [(4.)-299.2(doi:)-299.2(10.1126/s)5.5(cience.115801)7.1(3)]TJ -16.872 -1.2699 TD 0 Tc [(13)-9.6(7)-12.3(.)-507.7(Bal)-15(y)-10.7(a)0(n)-518.7(R)0(,)-521.1(G)0(u)-11.7(n)0(d)-518.9(R)0(,)-521.1(C)0(h)-14.9(a)0(w)-12.3(l)0(a)-514.9(A)-8.4(S,)-515.9(Kh)-20(are)-521.6(SP)-13.2(,)-515.2(P)0(r)-11.3(a)-9(d)-9.1(h)0(a)-14.7(n)-509.7(SJ)-11.3(,)-515.2(R)0(a)-14.8(n)0(e)-517(S)0(,)-523.5(e)0(t)-514.1(a)-9(l.)]TJ 2.1846 -1.2699 TD [(Co)-8.1(rr)-12.8(el)-14.3(at)-9.3(io)-11(n)-509.7(o)0(f)-516.7(C)-9.2(ell)-13.8(-)-8.8(S)0(u)-9.8(r)0(f)-10.2(a)-9(ce)-521.1(Cd)-10.8(8)-511.2(L)0(e)-13(v)0(e)-10.4(l)0(s)-512.3(W)0(i)-19.2(t)0(h)-512.5(F)-9.1(un)-12.4(cti)-12.2(on)-17.3(,)-507.7(P)0(h)-10.6(e)0(n)-18.1(oty)-17.5(pe)-515.4(a)-9(n)0(d)]TJ 0 -1.2624 TD [(Transcriptome)-356.5(of)-358(Naive)-365.9(Cd8)-355.7(T)-353.6(Cells.)]TJ /F11 1 Tf 15.587 0 TD (Immunology)Tj /F6 1 Tf 5.3443 0 TD [(\(2019\))-361.2(156\(4\):384)]TJ /F8 1 Tf 7.219 0 TD ()Tj /F6 1 Tf 0.514 0 TD (401.)Tj -28.6643 -1.2699 TD [(doi:)-301.1(10.1111/imm.13036)]TJ -2.1846 -1.2624 TD [(138.)-499.3(Eggert)-214.2(J,)-208.3(Au-Yeung)-217.9(BB.)-211(Functional)-210.6(Heterogeneity)-219(and)-210.4(Adaptation)-218.4(of)-206.8(Naive)-214.7(T)]TJ 2.1544 -1.2699 TD [(Cells)-263.7(in)-257.3(Response)-271.3(to)-256.3(Tonic)-261.8(Tcr)-261.4(Signals.)]TJ /F11 1 Tf 15.8289 0 TD [(Curr)-262.8(Opin)-260.5(Immunol)]TJ /F6 1 Tf 8.3151 0 TD [(\(2021\))-262.9(73:43)]TJ /F8 1 Tf 4.9966 0 TD ()Tj /F6 1 Tf 0.514 0 TD (9.)Tj -29.6546 -1.2624 TD [(doi:)-301.1(10.1016/j.coi.2021.09.007)]TJ -2.1544 -1.2699 TD [(139.)-499.3(Drobek)-343.1(A,)-349.8(Moudra)-341.9(A,)-342.3(Mueller)-345.9(D,)-345.6(Huranova)-344.6(M,)-340.8(Horkova)-347.1(V,)-347.4(Pribikova)-342.6(M,)]TJ 2.1544 -1.2699 TD [(et)-431(al.)-425.4(Strong)-436(Homeostatic)-426.4(Tcr)-427.7(Signals)-434.6(Induce)-428.8(Formation)-435.5(of)-426(Self-Tolerant)]TJ 0 -1.2624 TD [(Virtual)-284.3(Memory)-284.1(Cd8)-272.6(T)-285.5(Cells.)]TJ /F11 1 Tf 12.0946 0 TD [(EMBO)-282.3(J)]TJ /F6 1 Tf 3.5679 0 TD [(\(2018\))-278(37\(14\):e98518.)-281.4(doi:)-285.9(10.15252/)]TJ -15.6626 -1.2699 TD (embj.201798518)Tj -2.1544 -1.2624 TD [(140.)-499.3(Azzam)-217.8(HS,)-217(Grinberg)-221.4(A,)-221.3(Lui)-215.9(K,)-219.6(Shen)-213.5(H,)-216.3(Shores)-221.9(EW,)-217.4(Love)-219.1(PE.)-215.2(Cd5)-219.7(Expression)]TJ 2.1544 -1.2699 TD [(Is)-452(Developmentally)-456.3(Regulated)-451.3(by)-448(T)-451.8(Cell)-453.8(Receptor)-450.7(\(Tcr\))-452.3(Signals)-457.3(and)-444.7(Tcr)]TJ 0 -1.2624 TD (Avidity.)Tj /F11 1 Tf 3.4697 0 TD [(J)-300.3(Exp)-300.1(Med)]TJ /F6 1 Tf 4.4826 0 TD [(\(1998\))-300.7(188\(12\):2301)]TJ /F8 1 Tf 8.1261 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(11.)-298(doi:)-308.6(10.1084/jem.188.12.2301)]TJ 16.033 84.8666 TD [(141.)-499.3(Cho)-225.5(JH,)-226.9(Kim)-219.8(HO,)-225.7(Surh)-226(CD,)-226.3(Sprent)-223.7(J.)-223.5(T)-225.1(Cell)-227.1(Receptor-Dependent)-231.2(Regulation)]TJ 2.1544 -1.2699 TD [(of)-221.9(Lipid)-222.1(Rafts)-221.9(Controls)-219.4(Naive)-222.3(Cd8+)-222.1(T)-217.5(Cell)-219.5(Homeostasis.)]TJ /F11 1 Tf 22.3826 0 TD (Immunity)Tj /F6 1 Tf 4.1878 0 TD [(\(2010\))-217.5(32)]TJ -26.5704 -1.2624 TD (\(2\):214)Tj /F8 1 Tf 2.8271 0 TD ()Tj /F6 1 Tf 0.5065 0 TD [(26.)-305.6(doi:)-301.1(10.1016/j.immuni.2009.11.014)]TJ -5.4879 -1.2699 TD [(142.)-499.3(Fulton)-247(RB,)-248(Hamilton)-242.6(SE,)-248.7(Xing)-242.8(Y,)-245.5(Best)-247.5(JA,)-247(Goldrath)-243.1(AW,)-251.1(Hogquist)-241.6(KA,)-250.7(et)-242(al.)]TJ 2.1544 -1.2624 TD [(The)-313.7(Tcr's)-305.9(Sensitivity)-317.9(to)-309.2(Self)-306(Peptide-Mhc)-313.4(Dictates)-311.6(the)-308.2(Ability)-314.2(of)-305.1(Naive)-313(Cd8)]TJ 0 -1.2699 TD [(\(+\))-238.7(T)-225.1(Cells)-233.5(to)-233.6(Respond)-236.5(to)-233.6(Foreign)-236.8(Antigens.)]TJ /F11 1 Tf 17.6053 0 TD [(Nat)-227.9(Immunol)]TJ /F6 1 Tf 5.6164 0 TD [(\(2015\))-232.7(16\(1\):107)]TJ /F8 1 Tf 6.6143 0 TD ()Tj /F6 1 Tf -29.836 -1.2699 TD [(17.)-305.6(doi:)-301.1(10.1038/ni.3043)]TJ -2.1544 -1.2624 TD [(143.)-499.3(Cho)-338.8(JH,)-332.8(Kim)-340.8(HO,)-339.1(Ju)-329.7(YJ,)-339.3(Kye)-334.7(YC,)-337.9(Lee)-337.8(GW,)-335.9(Lee)-337.8(SW,)-334(et)-340.3(al.)-334.7(Cd45-Mediated)]TJ 2.1544 -1.2699 TD [(Control)-265.9(of)-267.3(Tcr)-261.4(Tuning)-271(in)-264.8(Naive)-260.1(and)-270.8(Memory)-261.4(Cd8\(+\))-269.4(T)-262.9(Cells.)]TJ /F11 1 Tf 24.8772 0 TD [(Nat)-265.7(Commun)]TJ /F6 1 Tf -24.8772 -1.2624 TD [(\(2016\))-300.7(7:13373.)-303.2(doi:)-301.1(10.1038/ncomms13373)]TJ -2.1544 -1.2699 TD [(144.)-499.3(Wiede)-337.8(F,)-335.4(La)-332.2(Gruta)-337.4(NL,)-333.7(Tiganis)-339.1(T.)-339.7(Ptpn2)-332.4(Attenuates)-339.1(T-Cell)-332.5(Lymphopenia-)]TJ 2.1544 -1.2624 TD 0.0452 Tc [(Induced)-546(Proliferation.)]TJ /F11 1 Tf 10.5753 0 TD 0.0437 Tc [(N)-7.7(a)3.6(t)-546.3(C)-4.1(ommu)-7.4(n)]TJ /F6 1 Tf 6.705 0 TD 0.0432 Tc [(\(2)-6.9(014)-6.9(\))-543.6(5)-6.9(:307)-6.9(3.)-547.6(doi:)-547.6(1)-6.9(0)0.6(.103)-6.9(8/)]TJ -17.2802 -1.2699 TD 0 Tc (ncomms4073)Tj -2.1544 -1.2699 TD 0.0257 Tc [(14)5.8(5.)-497.1(M)3.6(i)-1.5(l)3.6(a)1.6(m)-522.9(A)-5.4(AV)4.6(,)-527.3(B)4(artl)3.6(e)3.3(s)-3.4(o)4.1(n)-521.8(JM,)-519.8(B)-3.6(uc)]TJ 16.5772 0 TD 0.0233 Tc [(k)-523.3(M)-6.4(D,)-529.7(Cha)-8.4(n)4.9(g)-531.6(C)-1(H)4.7(,)-529.7(Sergushic)-6.7(h)2.5(e)-6.7(v)-524.1(A,)]TJ -14.3246 -1.2624 TD 0 Tc [(Donermeyer)-403.9(DL,)-404.2(et)-400.8(al.)-402.7(Tonic)-405.4(Tcr)-405.1(Signaling)-401.3(Inversely)-406.3(Regulates)-403.2(the)-406.4(Basal)]TJ 0 -1.2699 TD 0.0154 Tc [(M)-6.7(e)0.5(t)-7.6(a)-1.1(bo)-6.2(li)-4.3(s)-6.1(m)-525.7(of)-525.1(Cd4)-4.5(\()-4.4(+\))-526(T)-519.6(C)-1.4(e)-7(l)0.8(l)-6.7(s)1.4(.)]TJ /F11 1 Tf 14.2566 0 TD 0.0203 Tc [(Imm)7.6(unohor)6.3(i)-4.5(z)5.4(o)-3(n)7(s)]TJ /F6 1 Tf 7.5667 0 TD 0.0196 Tc [(\(2020\))-514.3(4\(8\):485)]TJ /F8 1 Tf 6.6823 0 TD 0 Tc ()Tj /F6 1 Tf 0.5291 0 TD 0.0199 Tc (97.)Tj -29.0347 -1.2624 TD 0 Tc [(doi:)-301.1(10.4049/immunohorizons.2000055)]TJ -2.2526 -1.2699 TD [(146.)-499.3(Rogers)-216.9(D,)-209.5(Sood)-219.2(A,)-213.7(Wang)-211.4(H,)-216.3(van)-211.9(Beek)-212.5(JJP,)-216.3(Rademaker)-219.4(TJ,)-214.2(Artusa)-213.6(P,)-210.2(et)-211.8(al.)-213.7(Pre-)]TJ 7.4999 0 0 7.4999 322.2991 540.9636 Tm [(Existing)-345.3(Chromatin)-336.5(Accessibility)-345.9(and)-338.9(Gene)-345.5(Expression)-342.7(Dif)63(ferences)-343.9(Among)]TJ T* [(N)-9.4(a)-9(ive)-521.4(C)-9.2(d)-9.1(4\()-17.1(+\))-521.2(T)-512.3(C)0(e)-8.9(l)0(l)-14(s)-512.9(In)]TJ /F7 1 Tf 10.8096 0 TD ()Tj /F6 1 Tf 0.5367 0 TD [(u)-9.1(e)0(n)-10.6(c)0(e)-521.1(E)-12.5(f)56.7(f)0(e)-11.1(c)0(t)-15.2(o)0(r)-519.3(P)0(o)-11.4(t)-7.9(en)-18.1(t)-7.9(i)0(a)-13.6(l)0(.)]TJ /F11 1 Tf 10.8549 0 TD 0.0109 Tc [(Ce)10.9(l)-5.2(l)-498.5(Re)10.9(p)]TJ /F6 1 Tf 4.029 0 TD 0.013 Tc [(\(2)13(02)13(1\))-498.2(3)13(7)]TJ -26.2303 -1.2699 TD 0 Tc [(\(9\):110064.)-302.3(doi:)-308.6(10.1016/j.celrep.2021.110064)]TJ -2.1544 -1.2624 TD 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T cell receptor, T cell differentiation and function, cytotoxic T lymphocyte (CTL) 2022-07-12T07:31:42+08:00 2022-07-12T07:31:42+08:00 Arbortext Advanced Print Publisher 10.0.1306/W Unicode application/pdf Arianne C. 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00000 n 0002057648 00000 n 0002057683 00000 n 0002057878 00000 n 0002057957 00000 n 0002062212 00000 n trailer <> startxref 116 %%EOF 709 0 obj<> endobj 710 0 obj<> endobj 711 0 obj<> endobj 718 0 obj<> endobj 863 0 obj<> endobj 864 0 obj<>stream Acrobat Distiller 7.0 (Windows) CD8 T cell, heterogeneity, stochasticity, TCR - T cell receptor, T cell differentiation and function, cytotoxic T lymphocyte (CTL) 2022-07-12T07:31:42+08:00 2022-07-12T10:47:55+08:00 Arbortext Advanced Print Publisher 10.0.1306/W Unicode 2022-07-12T10:47:55+08:00 application/pdf Arianne C. Richard The advent of technologies that can characterize the phenotypes, functions and fates of individual cells has revealed extensive and often unexpected levels of diversity between cells that are nominally of the same subset Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8+ T Cell Responses CD8 T cell heterogeneity stochasticity TCR - T cell receptor T cell differentiation and function cytotoxic T lymphocyte (CTL) uuid:44acce16-ed73-4ea7-a81a-d7987bfe3717 uuid:da655747-d6c3-41b5-9189-ea77a03d83ef endstream endobj xref 709 3 0002077306 00000 n 0002077369 00000 n 0002077506 00000 n 718 1 0002077607 00000 n 863 2 0002077780 00000 n 0002078474 00000 n trailer <]/Prev 116 >> startxref 2083209 %%EOF