HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation
Francisco J. Quintana, Doron Gerber, Sally C. Kent, Irun R. Cohen, Yechiel Shai
Francisco J. Quintana, Doron Gerber, Sally C. Kent, Irun R. Cohen, Yechiel Shai
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Research Article AIDS/HIV

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 4

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FP inhibits the activation of human T cells. Human Ob1A12 cells were act...
FP inhibits the activation of human T cells. Human Ob1A12 cells were activated with their target peptide MBP85–99 and MGAR B cells, and proliferation (A), IL-13 secretion (B), and IFN-γ secretion (C) were assayed. The data are presented as mean inhibitions ± SD (n = 3 or more). The uninhibited T cell proliferative responses were 2440 ± 190 cpm; the background proliferation in the absence of antigen was 85 ± 12 cpm. IFN-γ secretion was 964 ± 149 pg/ml, and IL-13 secretion was 4992 ± 352 pg/ml for activated cells not incubated with FP or CP-2G. Two independent experiments gave similar results.