Diversity and dominance among TCR recognizing HLA-A2.1+ influenza matrix peptide in human MHC class I transgenic mice.
The TCR structures of CTL derived from HLA-A2.1 transgenic mice were analyzed to determine features important in the interaction of murine TCR 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 of six independently derived CTLs that were V beta 8.1-positive demonstrated a restricted set of D-N-J beta sequences and an apparently restricted set of alpha-chains. However, at least five other distinct alpha beta pairs were found among HLA-A2.1 + M1 peptide-specific CTL in the 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 previously identified human TCR sequences specific for the same Ag-MHC complex revealed that the dominant murine V alpha and V beta segments used were not the homologues of the dominant human V beta and V alpha segments used. These results together with the lack of interspecies conservation in the alpha- and beta-chain CDR3 regions demonstrate that the dominant TCR structures recognizing HLA-A2.1 + M1(57-68) are substantially different between mouse and humans. Different factors may influence Ag-driven selection of the dominant TCRs used in each species.
Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville 22908.
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Man
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Ridge
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Engelhard
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology
D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; C031540:M-protein, influenza virus; C488936:M1 protein, Influenza A virus; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins