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HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen

Academic Article
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Overview

authors

  • Bertoletti, A.
  • Ferrari, C.
  • Fiaccadori, F.
  • Penna, A.
  • Margolskee, R.
  • Schlicht, H. J.
  • Fowler, P.
  • Guilhot, S.
  • Chisari, Francis

publication date

  • December 1991

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

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.

subject areas

  • Antigens, CD8
  • B-Lymphocytes
  • Capsid
  • Cell Line
  • Cytotoxicity, Immunologic
  • Genetic Vectors
  • Hepatitis B
  • Hepatitis B virus
  • Herpesvirus 4, Human
  • Histocompatibility Antigens Class I
  • Histocompatibility Testing
  • Humans
  • Male
  • Open Reading Frames
  • Peptides
  • T-Lymphocytes, Cytotoxic
  • Transfection
  • Viral Core Proteins
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Research

keywords

  • ACUTE HEPATITIS
  • EUKARYOTIC EXPRESSION VECTOR
  • SYNTHETIC PEPTIDES
  • VIRAL IMMUNOLOGY
  • VIRAL PATHOGENESIS
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Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.88.23.10445

PubMed ID

  • 1660137
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Additional Document Info

start page

  • 10445

end page

  • 10449

volume

  • 88

issue

  • 23

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