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 (HBcAg 64–72 , C 64–72, ELMTLATWV). T2 binding assay showed that C 64–72 had high affinity to HLA-A*0201 molecule. Functionally, the peptide C 64–72 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 C 64–72 -pulsed T2 cells or autologous human dendritic cells (DCs) respectively. HLA-A*0201-C 64–72 tetramer staining revealed the presence of a significant population of C 64–72 -specific CTLs in C 64–72 -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 C 64–72 -pulsed autologous DCs. These results indicate that the newly identified epitope C 64–72 has potential to be used in the development of immunotherapeutic approaches to HBV infection.