title: Identification of HLA-A*0201-restricted CD8+ T-cell epitope C₆₄₋₇₂ from hepatitis B virus core protein.
abstract: The efficacy of a potential therapeutic vaccine against chronic hepatitis B virus (HBV) infection depends on the development of strong and multi-specific T cell responses. The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward HBV core antigen (HBcAg) has been shown to be critical for the outcomes of HBV chronic infection. In this study we have identified a previously undescribed HLA-A*0201-restricted HBcAg-specific CTL epitope (HBcAg₆₄₋₇₂, C₆₄₋₇₂, ELMTLATWV). T2 binding assay showed that C₆₄₋₇₂ had high affinity to HLA-A*0201 molecule. Functionally, the peptide C₆₄₋₇₂ could induce peptide-specific CTLs both in vivo (HLA-A2.1/K(b) transgenic mice) and in vitro (PBLs of healthy HLA-A2.1+ donors), as demonstrated by interferon-γ (IFN-γ) secretion upon stimulation with C₆₄₋₇₂-pulsed T2 cells or autologous human dendritic cells (DCs) respectively. HLA-A*0201-C₆₄₋₇₂ tetramer staining revealed the presence of a significant population of C₆₄₋₇₂-specific CTLs in C₆₄₋₇₂-stimulated CD8+ T cells. Furthermore, the peptide-specific cytotoxic reactivity and the production of perforin and granzyme B of CTLs also increased after stimulation with C₆₄₋₇₂-pulsed autologous DCs. These results indicate that the newly identified epitope C₆₄₋₇₂ has potential to be used in the development of immunotherapeutic approaches to HBV infection.
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. lqy1969@yahoo.com.cn
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Liu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
authors.forename: Qinchun
authors.initials: Q
authors.lastname: Tan
authors.forename: Xinping
authors.initials: X
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D053804:Granzymes / Q000096:biosynthesis; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D054353:Perforin / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D014758:Viral Core Proteins; D054353:Perforin; D053804:Granzymes