Degenerate immunogenicity of an HLA-A2-restricted hepatitis B virus nucleocapsid cytotoxic T-lymphocyte epitope that is also presented by HLA-B51.
The 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 entirely within the HLA-A2-restricted HBc18-27 epitope. Here we show that HLA-B51-restricted cytotoxic T lymphocytes specific for HBc19-27 from a patient with 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 that peptide, implying that HBc18-27 can be presented by HLA-B51 as well as by HLA-A2. These results demonstrate the concept of degenerate immunogenicity across HLA class supertype boundaries in a human viral disease setting. In addition, they could facilitate the development of an epitope-based therapeutic vaccine to terminate chronic HBV infection that could provide a broad and diverse population coverage with a single peptide.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
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Thimme
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Chang
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Pemberton
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D000208:Acute Disease; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D017353:Gene Deletion; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D059949:HLA-B51 Antigen; D006509:Hepatitis B / Q000276:immunology / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D019251:Nucleocapsid / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016707:Tissue Fixation
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D010455:Peptides