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Related Experiment Videos

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

P J Norris1, M Sumaroka, C Brander

  • 1Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

Journal of Virology
|September 18, 2001
PubMed
Summary

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Human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells show potent antiviral activity. These cells, targeting the Gag protein, exhibit proliferation, IFN-gamma secretion, and perforin-mediated cytolysis.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells are crucial for controlling viral load.
  • The exact functional capabilities and targeted epitopes of these cells require further elucidation.

Purpose of the Study:

  • To characterize the functional attributes of Gag-specific CD4(+) T-cell clones from HIV-1-infected individuals.
  • To identify specific T helper cell epitopes within the HIV-1 Gag protein.
  • To investigate the mechanism of T cell-mediated cytotoxicity against HIV-1-infected cells.

Main Methods:

  • Generation of Gag-specific CD4(+) T-cell clones from HIV-1-infected individuals.
  • Peptide mapping to identify minimal T helper epitopes within the Gag protein.

Related Experiment Videos

  • Assessment of T cell proliferation, cytokine secretion (IFN-gamma), and cytolytic activity.
  • Mechanism of action studies using inhibitors (concanamycin A, EGTA, brefeldin A) and anti-Fas antibody.

    • Main Results:

    • Identification of multiple Gag-specific T helper epitopes, including a minimal epitope (VHAGPIAG) in the cyclophilin binding domain.
    • T cell clones demonstrated antigen-specific proliferation, IFN-gamma secretion, and perforin-mediated cytolysis.
    • Evidence of serine esterase release, indicating perforin-mediated cytotoxicity.

    Conclusions:

    • HIV-1 Gag protein harbors multiple T helper epitopes recognized by CD4(+) T cells.
    • T helper cells possess cytolytic capabilities, potentially contributing to the overall antiviral response against HIV-1.
    • Perforin-mediated cytotoxicity is a key mechanism employed by these Gag-specific T helper cells.