IMMUNODOMINANCE CORRELATES WITH T-CELL RECEPTOR (ALPHA-BETA) GENE USAGE IN THE CLASS II-RESTRICTED RESPONSE TO IN INFLUENZA HEMAGGLUTININ

Class II-restricted T-cell clones elicited by natural infection with i nfluenza A virus (H3N2 subtype) exhibit extensive diversity in their r ecognition specificity for the envelope glycoprotein, haemagglutinin, and focus on hypervariable regions of the HA1 subunit that feature in antigenic drift. However, T-cell clones established from the same indi vidual focus on a single antigenic site with differing fine specificit y for mutant viruses. We wished to determine whether such diversity of the haplotype and contrasting immunodominance of the individual's rep ertoire was mirrored in T-cell receptor (TcR) gene usage. A structural analysis was undertaken of the alpha and beta chains of TcR from a pa nel of CD4(+) T-cell memory clones established in vitro after natural infection with X31 virus and specific for eight distinct antigenic sit es of the HA1 subunit: p48-67 (A(k)), p58-73 (A(d)), p120-139 (A(k)), p177-199 (A(d)), p186-200 (A(d)), p226-245 (E(k)), p246-265 (E(k)) and p269-288 (A(k)). Direct sequencing of the a and P chains, using the p olymerase chain reaction, revealed that T-cell clones derived from the same donor used identical V-beta D-beta J(beta) and V-alpha J(alpha) elements. Moreover there was extensive diversity in usage of V-beta (V (beta)1 or V(beta)4 or V(beta)8) genes between individual mice, in ass ociation with diverse J(beta) and V-alpha J(alpha) elements for the re cognition of a common antigenic peptide. We conclude that the CD4(+) T -cell memory repertoire of the individual, following primary exposure to infectious virus, is oligoclonal and recruited from a limited numbe r of precursor cells.