Identification of hepatitis C virus (HCV) 2a-derived epitope peptides having the capacity to induce cytotoxic T lymphocytes in human leukocyte antigen-A24+ and HCV2a-infected patients

Cell Immunol. 2006 May;241(1):38-46. doi: 10.1016/j.cellimm.2006.07.009. Epub 2006 Sep 11.

Abstract

Since virus-specific cytotoxic T lymphocytes (CTLs) play a critical role in preventing the spread of hepatitis C virus (HCV), vaccine-based HCV-specific CTL induction could be a promising strategy to treat HCV-infected patients. In this study, we tried to identify HCV2a-derived epitopes, which can induce human leukocyte antigen (HLA)-A24-restricted and peptide-specific CTLs. Peripheral blood mononuclear cells of HCV2a-infected patients or healthy donors were stimulated in vitro with HCV2a-derived peptides, which were prepared based on the HLA-A24 binding motif. As a result, three peptides (HCV2a 576-584, HCV2a 627-635, and HCV2a 1085-1094) efficiently induced peptide-specific CTLs from HLA-A24(+) HCV2a-infected patients as well as healthy donors. The cytotoxicity was exhibited by peptide-specific CD8(+) T cells in an HLA-A24-restricted manner. In addition, the HCV2a 627-635 peptide was frequently recognized by immunoglobulin G of HCV2a-infected patients. These results indicate that the identified three HCV2a peptides might be applicable to peptide-based immunotherapy for HLA-A24(+) HCV2a-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A Antigens / biosynthesis*
  • HLA-A Antigens / blood
  • HLA-A24 Antigen
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / metabolism
  • Humans
  • Lymphocyte Activation / immunology
  • Peptide Fragments / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / virology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology*

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Peptide Fragments