Relationship between peptide binding and T cell epitope selection: a study with subtypes of HLA-B27 |
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Authors: | Lamas JR; Brooks JM; Galocha B; Rickinson AB; Lopez de Castro JA |
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Institution: | Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain. |
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Abstract: | 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.
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