The somatically generated T cell receptor CDR3a contributes to the MHC allele specificity of the T cell receptor

Mature T cells bearing ab T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor b chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor a and b chain and, surprisingly, dramatically affected by the non germ line encoded CDR3 of the T cell receptor a chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species. Naïve CD4 T cells were isolated from mice expressing a single T cell receptor b chain and one of 3 different alleles of MHCII. The T cell receptor a chains on these cells were sequenced and their sequences compared. Comparisons were also made in the use of different elements, the TRAVs, TRAJs and non germ line encoded CDR3 of the T cell receptor alpha chains.