Immunodominance correlates withT-cell receptor (ap) geneusageinthe class TI-restricted response toinfluenza haemagglutinin

SUMMARY Class II-restricted T-cell clones elicited bynatural infection withinfluenza Avirus (H3N2subtype) exhibit extensive diversity intheir recognition specificity fortheenvelope glycoprotein, haemagglutinin, andfocus onhypervariable regions oftheHAlsubunit thatfeature inantigenic drift. However, T-cell clones established fromthesameindividual focus onasingle antigenic site withdiffering fine specificity formutant viruses. Wewished todetermine whether suchdiversity of thehaplotype andcontrasting immunodominance oftheindividual's repertoire wasmirrored inTcell receptor (TcR) geneusage. A structural analysis wasundertaken oftheaandfchains ofTcR fromapanel ofCD4+T-cell memoryclones established invitro after natural infection withX31 virus andspecific foreight distinct antigenic sites oftheHAlsubunit: p48-67(Ak), p58-73(Ad), p120-139 (Ak), pl77-199 (Ad), pl86-200 (Ad), p226-245 (Ek), p246-265 (Ek) andp269-288 (Ak). Direct sequencing oftheaandPchains, using thepolymerase chain reaction, revealed that T-cell clones derived fromthesamedonorusedidentical VpDpJf, andVc, Ja, elements. Moreover there wasextensive diversity inusageofVp(VpI orV64orVp68) genes between individual mice, in association withdiverse J# andVa,Ja, elements fortherecognition ofacommonantigenic peptide. We conclude thattheCD4+T-cell memoryrepertoire oftheindividual, following primary exposure toinfectious virus, isoligoclonal andrecruited fromalimited numberofprecursor cells.