A novel cytotoxic T-cell epitope presented by HLA-A24 molecule in hepatitis C virus infection

Background/Aims: It has been suggested that cytotoxic T lymphocytes (CTL) h ave crucial roles for the hepatocellular damage in hepatitis C virus (HCV) infection. A series of CTL epitopes located in the HCV protein have been id entified. However, no CTL epitopes restricted by HLA-A24, a common HLA alle le in humans, has been identified. Methods: Peripheral blood and liver infiltrating mononuclear cells from the patients with hepatitis C virus infection and healthy controls were stimul ated with a series of peptides containing HLA-A24 binding motifs located in HCV protein. Results: An immunodominant HLA-A24 restricted CTL epitope (A24-4; AYSQQTRGL , amino acids 1031-1039) presented by HLA-A24 molecule was identified using a series of synthetic peptides containing the HLA-A24 binding motifs, The CTL activity against this peptide was induced both in peripheral blood and liver infiltrating mononuclear cells from HLA-A24-positive chronic hepatiti s C patients, not from HLA-A24-negative patients and HLA-A24-positive healt hy controls, CTL activity was blocked by anti-HLA-A24 and anti-CD8 antibodi es, not by anti-CD4 antibody. Furthermore, the A24-4-specific CTL recognize d the HCV gene transfected target cells. Conclusions: Because this peptide is presented by a common HLA class I mole cule, it might be useful for protection against hepatocellular damage and v accine development in large population of the HCV-infected patients. (C) 20 01 European Association for the Study of the Liver. Published by Elsevier S cience B.V. All rights reserved.