Contribution of HLA class I allele expression to CD8+ T-cell responses against Epstein-Barr virus

Most immune responses to viral infections involve CD8(+) T cells recognizing viral peptides of typically 9-10 amino acids in the groove of major histocompatibility complex (MHC) class I. Importantly, CD8(+) T-cell responses appear to focus on few viral epitopes, a phenomenon termed immuno-dominance. While the understanding of this phenomenon has been based largely on experimental mice models, it is imperative to evaluate its contribution in humans, as the design of peptide-based vaccines may be influenced by immunodomination. Here, we present evidence that immunodominance can be detected among Epstein-Barr virus (EBV) epitopes associated with two of the most frequent class I alleles in Western Europe, human leucocyte antigen (HLA)-A2 and HLA-B7. CD8(+) T-cell responses to HLA-A2-associated EBV epitopes were significantly reduced in individuals coexpressing HLA-B7. The impairment of HLA-A2-associated responses correlated with a dominant response to an HLA-B7 epitope. The data demonstrate a hierarchy in the human cellular immune response to immunodominant EBV epitopes presented by separate HLA class I alleles. This may have implications for EBV vaccine development as well as for the interpretation of isolated analysis of immunodominant responses to EBV.