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 by comparing the binding of three Epstein-Barr virus-derived peptide epitopes to HLA-B27 subtypes with their immunogenicity and antigenicity in the context of these subtypes. The effect of altering the major anchor residue Arg2 on binding or on recognition by peptide-specific cytotoxic T lymphocytes (CTL) was also examined. The three peptides bound significantly to all the B*2701-B*2706 subtypes. This did not correlate 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 B*2702- or B*2705-restricted responses bound to these subtypes less efficiently than one peptide that was immunogenic only in the B*2704 context. Thus, among several potentially immunogenic peptides from the same virus, the antiviral response is not necessarily directed against the one that binds best to the restricting subtype. These results indicate that HLA-B27 polymorphism influences antigen presentation in ways other than simply peptide affinity. Synthetic analogues lacking the canonical Arg2 motif of HLA-B27-bound peptides, even when binding much worse to the restricting subtype, were recognized equally by CTL specific for the parental peptide. This indicates that Arg2 is not required to maintain the structure of the epitope. The implications of these results for pathogenetic models of HLA-B27-associated disease are discussed.
Lamas
J R
JR
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain.
Brooks
J M
JM
Galocha
B
B
Rickinson
A B
AB
López de Castro
J A
JA
D017951:Antigen Presentation; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015796:HLA-B27 Antigen; D010446:Peptide Fragments