RELATIONSHIP BETWEEN PEPTIDE BINDING AND T-CELL EPITOPE SELECTION - ASTUDY WITH SUBTYPES OF HLA-B27

The effect of HLA-B27 polymorphism on antigen presentation was analyse d by comparing the binding of three Epstein-Barr virus-derived peptide epitopes to HLA-B27 subtypes with their immunogenicity and antigenici ty in the context of these subtypes. The effect of altering the major anchor residue Arg2 on binding or on recognition by peptide-specific c ytotoxic T lymphocytes (CTL) was also examined, The three peptides bou nd significantly to all the B2701-B*2706 subtypes, This did not corre late with the peptides being immunogenic or recognized by specific CTL in the context of only particular subtypes, In addition, of the three viral epitopes tested, those that were immunogenic in B2702- or B*27 05-restricted responses bound to these subtypes less efficiently than one peptide that was immunogenic only in the B2704 context, Thus, amo ng several potentially immunogenic peptides from the same virus, the a ntiviral response is not necessarily directed against the one that bin ds best to the restricting subtype. These results indicate that HLA-B2 7 polymorphism influences antigen presentation in ways other than simp ly peptide affinity. Synthetic analogues lacking the canonical Arg2 mo tif of HLA-B27-bound peptides, even when binding much worse to the res tricting subtype, were recognized equally by CTL specific for the pare ntal peptide, This indicates that Arg2 is not required to maintain the structure of the epitope, The implications of these results for patho genetic models of HLA-B27-associated disease are discussed.