Dominant TCR Vα usage by virus and tumor-reactive T cells with wide affinity ranges for their specific antigens

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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 Vα region, even though they expressed highly diverse TCR β chains and V(D)J junctional sequences. Functional assays and peptide/MHC multimer binding studies indicated that this restricted Vα usage was not associated with the affinity/avidity of the CTL clones. The Vα 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 Vα CDR.

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