Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome
ABSTRACT We have focused on conserved regions of the hepatitis C Virus (HCV) genome to identify viral peptides that contain HLA class I binding motifs and bind with high affinity to the corresponding purified HLA molecules. Accordingly, we have identified 31 candidate epitopes in the HCV that have the potential to be recognized by either HLA-A1-, A2.1-, A3-, A11- or A24-restricted cytotoxic T lymphocytes (CTL). Twelve conserved peptides that bind HLA-A2.1 with high or intermediate affinity were tested for immunogenicity in vitro in human primary CTL cultures and in vivo by direct immunization of HLA-A2.1/Kb transgenic mice. Six HLA-A2.1-restricted CTL epitopes were immunogenic in both systems. At least three of these peptide epitopes were endogenously processed and presented for CTL recognition. Overall, these data illustrate the value of this approach for the development of virus-specific, peptide-based vaccines.
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ABSTRACT: There is a strong epidemiologic relationship between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma, although the cellular and molecular mechanisms of tumor formation remain to be firmly established. Clearly, HCV is associated with the development of chronic hepatitis and cirrhosis, so it may contribute to hepatocarcinogenesis as a consequence of its central role in the appearance and progression of necroinflammatory liver disease. There is also increasing evidence for a direct contribution of several HCV gene products to the development of the transformed phenotype, although none of the putative mechanisms involved in tumor formation have been strongly supported by in vivo evidence. Even if HCV is not shown to be a complete carcinogen, it may act as a co-carcinogen with underlying (serologically negative) hepatitis B virus infection, in the context of alcoholic cirrhosis, and in patients with long term exposure to chemical hepatocarcinogens such as aflatoxin B1.Archivum Immunologiae et Therapiae Experimentalis 02/2001; 49 Suppl 2:S65-74. · 2.54 Impact Factor