Multiple effector functions mediated by human immunodeficiency virus-specific CD4(+) T-cell clones

J Virol. 2001 Oct;75(20):9771-9. doi: 10.1128/JVI.75.20.9771-9779.2001.

Abstract

Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain to be defined. In this study, we generated CD4(+) T-cell clones specific for Gag from HIV-1-infected persons with vigorous Gag-specific responses detectable in peripheral blood mononuclear cells. Multiple peptides containing T helper epitopes were identified, including a minimal peptide, VHAGPIAG (amino acids 218 to 226), in the cyclophilin binding domain of Gag. Peptide recognition by all clones examined induced cell proliferation, gamma interferon (IFN-gamma) secretion, and cytolytic activity. Cytolysis was abrogated by concanamycin A and EGTA but not brefeldin A or anti-Fas antibody, implying a perforin-mediated mechanism of cell lysis. Additionally, serine esterase release into the extracellular medium, a marker for cytolytic granules, was demonstrated in an antigen-specific, dose-dependent fashion. These data indicate that T helper cells can target multiple regions of the p24 Gag protein and suggest that cytolytic activity may be a component of the antiviral effect of these cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / pharmacology
  • Antibodies / pharmacology
  • Brefeldin A / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Clone Cells
  • Cyclophilins / immunology
  • Cytotoxicity, Immunologic / drug effects
  • Dose-Response Relationship, Drug
  • Egtazic Acid / pharmacology
  • Epitopes / immunology
  • HIV Core Protein p24 / chemistry
  • HIV Core Protein p24 / immunology
  • HIV Core Protein p24 / pharmacology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1*
  • Humans
  • Interferon-gamma / immunology
  • Macrolides*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Protein Binding
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • fas Receptor / immunology

Substances

  • Anti-Bacterial Agents
  • Antibodies
  • Epitopes
  • HIV Core Protein p24
  • Macrolides
  • fas Receptor
  • Brefeldin A
  • Egtazic Acid
  • concanamycin A
  • Interferon-gamma
  • Cyclophilins