Cellular immune response against HBV nucleocapsid antigen

点击翻译按钮获取中文摘要

It is generally believed that HLA class I restricted cytotoxic T lymphocytes (CTL) play an important role in hepatocellular injury during acute and chronic HBV infection. Recent studies have also suggested that hepatitis B virus (HBV) core region could be an immunological target. We established HBcAg-specific CTL from peripheral blood mononuclear cells (PBMC) or liver-infiltrating lymphocytes (LIL) of patients with chronic HBV infection using selected five synthetic peptides. PBMC were obtained from 10 patients with chronic HBV infection. Five clones from PBMC and one clone from LIL displayd a cytotoxic respones (more than 10%). We concluded that HLA class I restricted CTL that recognize HBcAg are present among PBMC and LIL of patients with chronic HBV infection. In successive study, we examined the change of nucleotide esquence of a part of core region at 3 points (before, top, and after the exacerbation) in the time course of hepatitis B infection, and compared the diversity of amino acids. 6 chronic HBV carriers who experienced the exacerbation of their disease were selected and nt 2062-2364 (303bp) were sequenced from the sera. The mean substitution rate were higher in the second sera than in the first (4 out of 6 patients), and lower in the third sera than in the second (4 out of 6patients). No significant difference was found in the rate of deduced amino acid divergence for the ideal HLA-A2 binding motifs between patients bearing HLA-A2 and not bearing it. Although no specific amino acid substitution in respect to HLA-A2 was found, some amino acid tends to be substituted at high frequency. We are now investigating the effect of HBV mutant on the function of helper T lymphocytes. We believe that these results could lead us to the developemt of vaccine therapy against HBV infection.