DIVERSITY AND DOMINANCE AMONG TCR RECOGNIZING HLA-A2.1(-I TRANSGENIC MICE() INFLUENZA MATRIX PEPTIDE IN HUMAN MHC CLASS)

The TCR structures of CTL derived from HLA-A2.1 transgenic mice were a nalyzed to determine features important in the interaction of murine T CR with the HLA-A2.1 + influenza M1(57-68) peptide complex. V beta 8.1 was dominant in 9 of 11 murine CTL lines, although three other V beta segments were also represented. Sequencing of TCR cDNA from a group o f six independently derived CTLs that were V beta 8.1-positive demonst rated a restricted set of D-N-J beta sequences and an apparently restr icted set of alpha-chains. However, at least five other distinct (alph a beta pairs were found among HLA-A2.1 + M1 peptide-specific CTL in th e absence of these chains. Consideration of all TCR sequences obtained demonstrated diverse beta-chain CDR3 regions with some restriction in V alpha segment usage and bias in amino acid sequence of alpha-chain CDR3 regions. Nevertheless, the strongest correlation with HLA-A2.1 M1 specificity was clearly V beta 8.1 usage. Comparison with previousl y identified human TCR sequences specific for the same Ag-MHC complex revealed that the dominant murine V alpha and V beta segments used wer e not the homologues of the dominant human V beta and V alpha segments used. These results together with the lack of interspecies conservati on in the alpha- and beta-chain CDR3 regions demonstrate that the domi nant TCR structures recognizing HLA-A2.1 + M1(57-68) are substantially different between mouse and humans. Different factors may influence A g-driven selection of the dominant TCRs used in each species.