- 作者： Sun-Lung Tsai ; Pei-Jer Chen; Pei-Ming Yang; Ta-Hsiu Liao; Juei-Low Sung; Ming-Yang Lai; Jyh-HsiungHuang; Tong-Hsuan Chang; Ding-Shinn Chen
- 作者服務機構： a Department of Internal Medicine, and; b Hepatitis Research Center, National Taiwan University Hospital;; c Graduate Institute of Clinical Medicine, and; d Graduate Institute of Biochemistry, National Taiwan University College of; Medicine;; e Division of Cell Biology and Immunology, Development Center for Biotechnology, Taipei, Taiwan, Republic of China
- 中文摘要： --
- 英文摘要： T cell clones specific for hepatitis B core (HBcAg) and a (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 prefer- ential 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 (Thl) 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 Th 1 clones recognizing a determinant of HBcAg and HBeAg are present in the liver of chronic hepatitis B patients. The preferential Va 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.
- 中文關鍵字： --
- 英文關鍵字： Hepatitis B virus; Peptide antigen; T cell receptor
