Relationship between peptide binding and T cell epitope selection: a study with subtypes of HLA-B27

The effect of HLA-B27 polymorphism on antigen presentation was analysed bycomparing the binding of three Epstein-Barr virus-derived peptide epitopesto HLA-B27 subtypes with their immunogenicity and antigenicity in thecontext of these subtypes. The effect of altering the major anchor residueArg2 on binding or on recognition by peptide-specific cytotoxic Tlymphocytes (CTL) was also examined. The three peptides bound significantlyto all the B*2701-B*2706 subtypes. This did not correlate with the peptidesbeing immunogenic or recognized by specific CTL in the context of onlyparticular subtypes. In addition, of the three viral epitopes tested, thosethat were immunogenic in B*2702- or B*2705-restricted responses bound tothese subtypes less efficiently than one peptide that was immunogenic onlyin the B*2704 context. Thus, among several potentially immunogenic peptidesfrom the same virus, the antiviral response is not necessarily directedagainst the one that binds best to the restricting subtype. These resultsindicate that HLA- B27 polymorphism influences antigen presentation in waysother than simply peptide affinity. Synthetic analogues lacking thecanonical Arg2 motif of HLA-B27-bound peptides, even when binding muchworse to the restricting subtype, were recognized equally by CTL specificfor the parental peptide. This indicates that Arg2 is not required tomaintain the structure of the epitope. The implications of these resultsfor pathogenetic models of HLA-B27-associated disease are discussed.