HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation.
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-gamma 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.
Quintana
Francisco J
FJ
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Gerber
Doron
D
Kent
Sally C
SC
Cohen
Irun R
IR
Shai
Yechiel
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008561:Membrane Fusion / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015704:CD4 Antigens; D002273:Carcinogens; D015700:HIV Envelope Protein gp41; D007476:Ionophores; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate