Studies on the Immunopathogenesis of Viral Hepatitis C

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We studied on T-cell responses to hepatitis C virus (HCV) nucleoprotein in patients with chronic hepatitis C to clarify the immunopathogenic mechanisms of HCV infection. We demonstrated the presence of cytotoxic T lymphocytes (CTLs) in peripheral blood of patients with HCV infection. We successfully induced HLA B44-restricted HCV-specific CTLs and defined the minimal optimal epitope to be HCV nucleoprotein residues 88 to 96. We further demonstrated that HCV-specific helper T cells existed and stimulated activation and proliferation of CTLs. HCV mutates rapidly. but is classified into several genotypes. An amino acid sequence of HCV nucleoprotein residues 88 to 96 is conserved among HCV isolates except for residue 91. An amino acid at residue 91 is also conserved among the members of the same genotype of HCV.HLA B44-restricted HCV-specific CTLs could be induced by and recognized HCV of genotypes II/1b and III/2a, but neither I/1a nor IV/2b. A rare variant HCV of genotype I/1a, however, could induced HLA B44-restricted HCV-specific CTLs. The results contribute not only to elucidationof the immunopathogenic mechanisms of HCV infection but also to designing CTL vaccines to prevent HCV infection and eliminate HCV from infected patients with HLA B44.