T cell receptor specificity for major histocompatibility complex proteins

The ligands for alpha beta T cell receptors (αβTCRs) are usually major histocompatibility complex (MHC) proteins bound to peptides. Although there is evidence that T cell receptor variable regions have been selected evolutionarily to bind MHC, the rules governing this interaction have not previously been apparent. However, recent solved structures of T cell receptors with related variable regions bound to MHC plus peptides suggest that some amino acids in variable region CDR1 and CDR2s almost always react in a consistent way with MHC. These amino acids may therefore have been selected evolutionarily to predispose T cell receptors toward recognition of MHC ligands.