title: 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.
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) alpha chain variable (V(alpha)) gene was found: V(alpha)12.1 for five HLA-Cw9(3)-restricted cytotoxic T lymphocyte (CTL) clones, and V(alpha)7.1 for three other HLA-DRw52-restricted type 1 helper T cell (Th1) clones. Although heterogeneous in the usage of TCR alpha chain joining region (J(alpha)) 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 V(alpha) gene usage and the expression of conserved residues in junctional-region sequences of TCRalpha chains by viral-peptide-specific, intrahepatic T cells may provide a T cell mechanism of HBV immunopathogenesis. Copyright 1994 S. Karger AG, Basel
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: S.-L.
authors.initials: SL
authors.lastname: Tsai
authors.forename: P.-J.
authors.initials: PJ
authors.lastname: Chen
authors.forename: P.-M.
authors.initials: PM
authors.lastname: Yang
authors.forename: T.-H.
authors.initials: TH
authors.lastname: Liao
authors.forename: J.-L.
authors.initials: JL
authors.lastname: Sung
authors.forename: M.-Y.
authors.initials: MY
authors.lastname: Lai
authors.forename: J.-H.
authors.initials: JH
authors.lastname: Huang
authors.forename: T.-H.
authors.initials: TH
authors.lastname: Chang
authors.forename: D.-S.
authors.initials: DS
authors.lastname: Chen