HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein.
Cytotoxic T lymphocytes have been reported to be involved in the immune clearance of virus-infected cells and in the pathogenesis of viral infection. We studied the cytotoxic T lymphocyte response to the putative nucleocapsid protein of hepatitis C virus in patients with chronic hepatitis C. Cytotoxic T lymphocytes specific for hepatitis C virus nucleocapsid protein were generated from peripheral blood lymphocytes by means of repeated stimulation with a synthetic hepatitis C virus nucleocapsid protein peptide. The cytotoxic T lymphocytes were CD8 positive and recognized an epitope in hepatitis C virus nucleocapsid protein residues 81 to 100 in association with a human leukocyte antigen class I molecule, B44. The peptide-induced cytotoxic T lymphocytes recognized target cells synthesizing hepatitis C virus nucleocapsid protein endogenously, though less efficiently than peptide-pulsed target cells. The human leukocyte antigen B44-restricted cytotoxic T lymphocyte response was observed in three of five patients with chronic hepatitis C and a human leukocyte antigen B44 molecule but in neither of two hepatitis C virus-negative healthy individuals with human leukocyte antigen B44 molecules. The results demonstrate the presence of hepatitis C virus-specific cytotoxic T lymphocytes in the peripheral blood of patients with chronic hepatitis C and provide a strategy to study the role of cytotoxic T lymphocytes in the viral clearance and the pathogenesis of hepatitis C virus infection.
Kita
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Moriyama
T
T
Kaneko
T
T
Harase
I
I
Nomura
M
M
Miura
H
H
Nakamura
I
I
Yazaki
Y
Y
Imawari
M
M
D000956:Antigens, Viral / Q000276:immunology*; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D015235:HLA-B Antigens / Q000502:physiology*; D059948:HLA-B44 Antigen; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus