Polymorphism Within a TCRAV Family Influences the Repertoire Through Class I/II Restriction

Abstract

Antibody-staining experiments have shown that closely related members of the TCRAV3 family are reciprocally selected into the CD4 or CD8 peripheral T cell subsets. This has been attributed to the individual AV3 members interacting preferentially with either MHC class I or MHC class II molecules. Single amino acid residues present in the complementarity-determining regions (CDR) CDR1α and CDR2α are important in determining MHC class specificity. We have now extended these observations to survey the expressed repertoire of the AV3 family in C57BL/6 mice. Three of the four expressed AV3 members are preferentially selected into the CD4+ subset of T cells. These share the same amino acid residue in both CDR1α and CDR2α that differ from the only CD8-skewed member. Preferential expression of an individual AV3 is not caused by other endogenous α- or β-chains, by any conserved CDR3 sequence, or by the usage of TCRAJ regions. This study shows that residues in the CDR1 and CDR2 regions are primary determinants for MHC class discrimination and suggests that polymorphism found within a TCRAV family has an important effect on the overall shaping of the T cell repertoire.