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.
Battaglia
Manuela
M
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI 53201-2178 USA.
Gorski
Jack
J
D000595:Amino Acid Sequence; D000818:Animals; D019674:Genes, T-Cell Receptor beta; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015804:HLA-DR4 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta