The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation

Abstract

Thousands of potentially antigenic peptides are encoded by an infecting pathogen; however, only a small proportion induce measurable CD8+T cell responses. To investigate the factors that control peptide immunogenicity, we have examined the cytotoxic T lymphocyte (CTL) response to a previously undefined epitope (77 APQPAPENAY86) from the BZLF1 protein of Epstein-Barr virus (EBV). This peptide binds well to two human histocompatibility leukocyte antigen (HLA) allotypes, HLA-B*3501 and HLA-B*3508, which differ by a single amino acid at position 156 ( 156 Leucine vs. 156 Arginine, respectively). Surprisingly, only individuals expressing HLA-B*3508 show evidence of a CTL response to the 77APQPAPE..