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Characterization of T cell clones specific to a determinant of hepatitis B virus core and e antigens in chronic type B hepatitis: Implication for a T cell mechanism of HBV immunopathogenesis

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Journal of Biomedical Science

Abstract

T cell clones specific for hepatitis B core (HBcAg) and e (HBeAg) antigens of hepatitis B virus (HBV) were generated from liver infiltrates of HBeAg-positive patients. Analyzed with a panel of overlapping synthetic peptides spanning the complete sequences of HBcAg and HBeAg, eight clones responded specifically to the e2 peptide (PAYRPPNAPIL; amino acid residues 130–140 of HBcAg and HBeAg), which was doubly restricted by class I and II molecules. A preferential usage of the T cell receptor (TCR) α chain variable (Vα) gene was found: Vα12.1 for five HLA-Cw9(3)-restricted cytotoxic T lymphocyte (CTL) clones, and Vα7.1 for three other HLA-DRw52-restricted type 1 helper T cell (Th1) clones. Although heterogeneous in the usage of TCR α chain joining region (Jα) segments, their junctional-region sequences revealed conserved hydrophilic serine residues in seven of the eight e2-specific T cell clones. Single alanine substitution of the centrally located and the only hydrophilic asparagine residue of e2 peptide abrogated T cell responsiveness. The nonstimulatory e2 analogue could competitively inhibit e2-specific responses. These results demonstrate that both CTL and Th1 clones recognizing a determinant of HBcAg and HBeAg are present in the liver of chronic hepatitis B patients. The preferential Vα gene usage and the expression of conserved residues in junctional-region sequences of TCRα chains by viral-peptide-specific, intrahepatic T cells may provide a T cell mechanism of HBV immunopathogenesis.

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China

    Sun-Lung Tsai, Pei-Ming Yang, Juei-Low Sung &  Ding-Shinn Chen

  2. Graduate Institute of Clinical Medicine, Taipei, Taiwan, Republic of China

    Pei-Jer Chen & Ming-Yang Lai

  3. Graduate Institute of Biochemistry, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China

    Ta-Hsiu Liao

  4. Division of Cell Biology and Immunology, Development Center for Biotechnology, Taipei, Taiwan, Republic of China

    Jyh-Hsiung Huang & Tong-Hsuan Chang

  5. Hepatitis Research Center, National Taiwan University Hospital, 1, Chang-Te Street, Taipei, Taiwan 10016 (Republic of China)

    Ding-Shinn Chen

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Tsai, SL., Chen, PJ., Yang, PM. et al. Characterization of T cell clones specific to a determinant of hepatitis B virus core and e antigens in chronic type B hepatitis: Implication for a T cell mechanism of HBV immunopathogenesis. J Biomed Sci 1, 105–118 (1994). https://doi.org/10.1007/BF02257984

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