Dramatic influence of V beta gene polymorphism on an antigen-specific CD8(+) T cell response in vivo

According to recent crystallographic studies, the TCR-alpha beta contacts M HC class I-bound antigenic peptides via the polymorphic V gene-encoded comp lementarity-determining region 1 beta (CDR1 beta) and the hypervariable (D) J-encoded CDR3 beta and CDR3 alpha domains. To evaluate directly the relati ve importance of CDR1 beta polymorphism on the fine specificity of T cell r esponses in vivo, we have taken advantage of congenic V beta(a) and V beta( b) mouse strains that differ by a CDR1 polymorphism in the V beta 10 gene s egment. The V beta 10-restricted CD8(+) T cell response to a defined immuno dominant epitope was dramatically reduced in Vpa compared with V beta(b) mi ce, as measured either by the expansion of V beta 10(+) cells or by the bin ding of MMC-peptide tetramers, These data indicate that Vp polymorphism has an important impact on TCR-ligand binding in vivo, presumably by modifying the affinity of CDR1 beta-peptide interactions.