Dominant TCR V alpha usage by virus and tumor-reactive T cells with wide affinity ranges for their specific antigens |
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Authors: | Trautmann Lydie Labarrière Nathalie Jotereau Francine Karanikas Vaios Gervois Nadine Connerotte Thierry Coulie Pierre Bonneville Marc |
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Institution: | INSERM U463, Institut de Biologie, Nantes, France. |
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Abstract: | We have studied the TCR features and functional responses of three sets of human cytolytic T cell (CTL) clones, recognizing antigenic peptides presented by HLA-A2 and derived from the Epstein-Barr virus proteins BMLF1 and BRLF1 and from the melanoma protein Melan-A/MART-1. Within each set, a majority of clones used a recurrent V alpha region, even though they expressed highly diverse TCR beta chains and V(D)J junctional sequences. Functional assays and peptide/MHC multimer binding studies indicated that this restricted V alpha usage was not associated with the affinity/avidity of the CTL clones. The V alpha dominance, which may be a frequent feature of antigen-specific T cells, likely reflects a restricted geometry of TCR/peptide/MHC complexes, primarily determined by V alpha CDR. |
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