Article

Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome

DOI:http://dx.doi.org/10.1093/intimm/8.5.651
Source: OAI

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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    Article: Chronic hepatitis C virus infection and the pathogenesis of hepatocellular carcinoma.
    M Feitelson
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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
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

31 candidate epitopes
 
A24-restricted cytotoxic T lymphocytes
 
bind HLA-A2.1
 
conserved regions
 
contain HLA class
 
corresponding purified HLA molecules
 
CTL
 
CTL recognition
 
direct immunization
 
HCV
 
hepatitis C Virus
 
HLA-A1-
 
HLA-A2.1-restricted CTL epitopes
 
human primary CTL cultures
 
immunogenicity
 
peptide-based vaccines
 
viral peptides
 
virus-specific
 
vitro