Evidence for preferred MHC class II-TCR recognition independent of the source of bound peptide

The interaction between TCR and peptide-MHC is well described in terms of the recognition of the peptide, but the recognition of the MHC is less well understood. At issue is whether particular V gene products may have higher affinity for some MHC over others and to what extent the bound peptide influences V gene selection. We examined this issue by developing T cell lines in which the presenting MHC class II molecule has a constant TCR contact region, while the presented peptides vary. If there is an affinity between particular V genes and the specific MHC used, only a subset of the V genes will be associated with the response. Indeed, in all the cell lines analyzed, there was a reproducible usage of a limited number of Vbeta genes, regardless of the bound peptides. This Vbeta-gene constraint was independent of the CDR3 sequence, compatible with the lack of involvement of specific peptides. Our results support the hypothesis that certain V gene products may have a preference for interacting with a particular MHC molecule, and this could have an impact in selectively controlling immune responses.