A novel cytotoxic T-cell epitope presented by HLA-A24 molecule in hepatitis C virus infection.
OBJECTIVE
It has been suggested that cytotoxic T lymphocytes (CTL) have crucial roles for the hepatocellular damage in hepatitis C virus (HCV) infection. A series of CTL epitopes located in the HCV protein have been identified. However, no CTL epitopes restricted by HLA-A24, a common HLA allele 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 stimulated 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 hepatitis C patients, not from HLA-A24-negative patients and HLA-A24-positive healthy controls. CTL activity was blocked by anti-HLA-A24 and anti-CD8 antibodies, not by anti-CD4 antibody. Furthermore, the A24-4-specific CTL recognized the HCV gene transfected target cells.


CONCLUSIONS
Because this peptide is presented by a common HLA class I molecule, it might be useful for protection against hepatocellular damage and vaccine development in large population of the HCV-infected patients.
Kurokohchi
K
K
Third Department of Internal Medicine, Faculty of Medicine, Kagawa Medical University, Kita-gun, Japan. kuroko@kms.ac.jp
Arima
K
K
Nishioka
M
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019138:Antibodies, Blocking; D017951:Antigen Presentation; D001665:Binding Sites; D016022:Case-Control Studies; D002460:Cell Line; D018604:Epitope Mapping; D015234:HLA-A Antigens / Q000378:metabolism*; D059871:HLA-A24 Antigen; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006511:Hepatitis B Antigens / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D019138:Antibodies, Blocking; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D006511:Hepatitis B Antigens; D016056:Immunodominant Epitopes