An HLA-B27 polymorphism (B*2710) that is critical for T-cell recognition has limited effects on peptide specificity

Abstract: The B2710 subtype differs from the HLA-B27 prototype (B2705) only by having Glu instead of Val at position 152, in the α2 helix of the peptide-binding site. In spite of its structural similarity most allore-active CTL raised against B2705 fail to cross-react with B2710. Indeed, of the residues that are polymorphic among HLA-B27 subtypes, the Val> Glu152 change has the greatest influence on HLA-B27 T-cell antigenicity. The molecular basis for this antigenic disparity was analyzed in this study. Sequence analysis indicated that B2710-bound peptides have very similar motifs to B2705-bound ones both at the main and auxiliary anchor positions. In addition, most of the individual ligands sequenced from B2710 were previously found in B2705. Together these results indicate that both subtypes have largely overlapping peptide repertoires. Molecular dynamics simulations of a common ligand in complex with either B2710 or B2705 failed to detect significant conformational changes in the peptidic main chain or in solvent accessibility of the side chains. In addition, modeling of the Val>Glu152 change into the MHC-peptide-TCR structure suggested a direct role of residue 152 in interaction with the TCR. Thus, the large differences in T-cell recognition between B2710 and B2705 are not explained by an effect of the Glu152 change on peptide specificity or conformation, but by different direct interactions with the TCR.

Journal article

An HLA-B27 polymorphism (B*2710) that is critical for T-cell recognition has limited effects on peptide specificity, Tissue Antigens 1998 51 (1), 1-9