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.
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Research Article AIDS/HIV Article has an altmetric score of 9

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

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

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Figure 6

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FP interacts with the TCR and does not inhibit T cell activation induced...
FP interacts with the TCR and does not inhibit T cell activation induced by PMA/ionomycin or antibodies to CD3. (A) A2b T cells were stimulated with PMA/ionomycin or (B) antibodies to CD3 (1 μg/ml) in the presence of FP or p277, and T cell proliferation was studied. (C) A2b T cells were incubated with FP-Rho or F9L-Rho overnight. Cells were cross-linked with DCC, and protein extracts were separated by SDS-PAGE and analyzed for rhodamine fluorescence. Total proteins were visualized by Coomassie brilliant blue. M, marker. (D) A2b T cells were incubated with FP-Rho or F9L-Rho for 1 hour, lysed, and immunoprecipitated with antibodies to TCR, CD28, actin, HSP60, or MHC I. Bound proteins were separated by SDS-PAGE and analyzed for the presence of the fluorescence-labeled peptides. (E) A2b T cells were incubated with FP-Rho or V2E-Rho for 1 hour, lysed, and immunoprecipitated with antibodies to TCR or MHC I. Bound proteins were separated by SDS-PAGE and analyzed for the presence of the fluorescence-labeled peptides.