Cellular immune response to core region protein of hepatitis C virus in patients with chronic hepatitis C

点击翻译按钮获取中文摘要

Evidence suggest that cellular immunity to HCV core protein may be important in the pathogenesis of viral infection. Therefore IFN-gamma production by peripheral blood mononuclear cells derived from patients with chronic HCV infection was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein. To identify the immunodominant epitopes, IFN-gamma production in responders was also assessed with a panel of synthetic peptides that covered the entire core region. Mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein ; asymptomatic HCV carriers demonstrated a lower response rate. Individuals who had received IFN-alpha treatment and went into clinical and virologic remission had a higher response rate compared to those with ongoing hepatitis who failed therapy. Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides ; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141-160 was recognized by 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141-160. Thus, the mononuclear cell response appeared to be HLA DR restricted and the responding cells were identified as CD4+T cells. This study indicates the presence of immunodominant T cell epitopes within HCV core protein in association with HLA DR phenotypes and provides an approach to investigate the role of CD4+ T cells in the pathogenesis of HCV associated liver disease.