Degenerate immunogenicity of an HLA-A2-restricted hepatitis B virus nucleocapsid cytotoxic T-lymphocyte epitope that is also presented by HLA-B51

re recent identification of hepatitis B virus (HBV) epitopes restricted by multiple HLA alleles has greatly expanded the epitope repertoire available for T-cell-mediated therapeutic vaccine development. The HLA-B51-restricted peptide HBc19-27 is particularly interesting because it is located entirel y within the HLA-A2-restricted HBc18-27 epitope. Here spe show that HLA-B51 -restricted cytotoxic T lymphocytes specific for HBc19-27 from a patient wi th acute HBV infection were also able to lyse HLA-B51-positive target cells pulsed with HBc18-27 and to produce gamma interferon when stimulated by th at peptide, implying that HBc18-27 can be presented by HLA-B51 as well as b y HLA-A2. These results demonstrate the concept of degenerate immunogenicit y across HLA class supertype boundaries in a human viral disease setting. I n addition, they could facilitate the development of an epitope-based thera peutic vaccine to terminate chronic HBV infection that could provide a broa d and diverse population coverage with a single peptide.