HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen.
- 1 December 1991
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 88 (23), 10445-10449
- https://doi.org/10.1073/pnas.88.23.10445
Abstract
Knowledge of the immune effector mechanisms responsible for clearance of hepatitis B virus (HBV)-infected cells has been severely limited by the absence of reproducible systems to selectively expand and to characterize HBV-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of patients with viral hepatitis. By using a strategy involving sequential stimulation with HBV nucleocapsid synthetic peptides followed by autologous, or HLA class I-matched, HBV nucleocapsid transfectants, we now report the existence of CTLs able to lyse target cells that express endogenously synthesized HBV nucleocapsid antigen in the peripheral blood of patients with acute viral hepatitis B. The CTL response is HLA-A2 restricted, mediated by CD8-positive T cells, and specific for a single epitope, located between amino acid residues 11 and 27 of HBV core protein; these residues are shared with the secretable precore-derived hepatitis B e antigen. Equivalent lysis of target cells that express each of these proteins suggests that their intracellular trafficking pathways may intersect. The current report provides definitive evidence that HLA class I-restricted, CD8-positive CTLs that recognize endogenously synthesized HBV nucleocapsid antigen are induced during acute HBV infection in humans and establishes a strategy that should permit a detailed analysis of the role played by HBV-specific CTLs in the immunopathogenesis of viral hepatitis.Keywords
This publication has 21 references indexed in Scilit:
- Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection.The Journal of Immunology, 1990
- Isolation of an endogenously processed immunodominant viral peptide from the class I H–2Kb moleculeNature, 1990
- Immunobiology and Pathogenesis of Hepatocellular Injury in Hepatitis B Virus Transgenic MiceScience, 1990
- Ouabain-resistant mutants of the rat Na,K-ATPase alpha 2 isoform identified by using an episomal expression vector.Molecular and Cellular Biology, 1990
- Hepatitis B virus structure and biologyMicrobial Pathogenesis, 1989
- DEFINITION OF HEPATITIS-B VIRUS (HBV)-SPECIFIC TARGET ANTIGENS RECOGNIZED BY CYTOTOXIC T-CELLS IN ACUTE HBV INFECTION1987
- VIRUS AND IMMUNE RESPONSES: LYMPHOCYTIC CHORIOMENINGITIS VIRUS AS A PROTOTYPE MODEL OF VIRAL PATHOGENESISBritish Medical Bulletin, 1985
- Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes.The Journal of Immunology, 1982
- Hepatitis B virus genes and their expression in E. coliNature, 1979
- T-Cell-Mediated Immunopathology in Viral InfectionsImmunological Reviews, 1974