Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation
Francisco J. Quintana, … , Irun R. Cohen, Yechiel Shai
Francisco J. Quintana, … , Irun R. Cohen, Yechiel Shai
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2149-2158. https://doi.org/10.1172/JCI23956.
View: Text | PDF
Research Article AIDS/HIV

HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation

  • Text
  • PDF
Abstract

The fusion peptide (FP) in the N terminus of the HIV envelope glycoprotein, gp41, functions together with other gp41 domains to fuse the virion with the host cell membrane. We now report that FP colocalizes with CD4 and TCR molecules, coprecipitates with the TCR, and inhibits antigen-specific T cell proliferation and proinflammatory cytokine secretion in vitro. These effects are specific: T cell activation by PMA/ionomycin or mitogenic antibodies is not affected by FPs, and FPs do not interfere with antigen-presenting cell function. In vivo, FPs inhibit the activation of arthritogenic T cells in the autoimmune disease model of adjuvant arthritis and reduce the disease-associated IFN-γ response. Hence, FPs might play 2 roles in HIV infection: mediating membrane fusion while downregulating T cell responses to itself that could block infection. Disassociated from HIV, however, the FP molecule provides a novel reagent for downregulating undesirable immune responses, exemplified here by adjuvant arthritis.

Authors

Francisco J. Quintana, Doron Gerber, Sally C. Kent, Irun R. Cohen, Yechiel Shai

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
HIV-1 gp41 extracellular domain. The extracellular portion of gp41 (aa 5...
HIV-1 gp41 extracellular domain. The extracellular portion of gp41 (aa 512–684) contains a number of functional domains: gp41 becomes active after gp120 (aa 1–511) binds to surface receptors; FP inserts into the membrane of the target cell; C20 inserts into the membrane of the virion; N36 and C34 form a 6-helix bundle “spring” that brings the membranes into apposition; and ISU is immunosuppressive. TM, gp41 transmembrane domain.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts