HLA B44–restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein

• Published in: Hepatology (Baltimore, Md.) Md.), 1993-11, Vol.18 (5), p.1039-1044
• Main Authors: Kita, Hiroto, Moriyama, Takashi, Kaneko, Takashi, Harase, Ichiro, Nomura, Masayuki, Miura, Hideaki, Nakamura, Ikuo, Yazaki, Yoshio, Imawari, Michio
• Format: Article
• Language: English
• Subjects: Antigens, Viral - immunology; Biological and medical sciences; Chronic Disease; Cytotoxicity, Immunologic; Epitopes - immunology; Hepacivirus - immunology; Hepatitis C - immunology; HLA-B Antigens - physiology; HLA-B44 Antigen; Human viral diseases; Humans; Infectious diseases; Medical sciences; T-Lymphocytes, Cytotoxic - immunology; Viral Core Proteins - immunology; Viral diseases; Viral hepatitis
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840180504

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 peptideinduced 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. (HEPATOLOGY 1993;18:1039‐1044).