A highly conserved sequence associated with the HIV gp41 loop region is an immunomodulator of antigen-specific T cells in mice

Avraham Ashkenazi, Omri Faingold, Nathali Kaushansky, Avraham Ben-Nun, Yechiel Shai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Modulation of T-cell responses by HIV occurs via distinct mechanisms, 1 of which involves inactivation of T cells already at the stage of virus-cell fusion. Hydrophobic portions of the gp41 protein of the viral envelope that contributes to membrane fusion may modulate T-cell responsiveness. Here we found a highly conserved sequence (termed "ISLAD") that is associated with the membranotropic gp41 loop region. We showed that ISLAD has the ability to bind the T-cell membrane and to interact with the T-cell receptor (TCR) complex. Furthermore, ISLAD inhibited T-cell proliferation and interferon-g secretion that resulted from TCR engagement through antigen-presenting cells. Moreover, administering ISLAD (10 mg per mouse) to an experimental autoimmune encephalomyelitis (EAE)model ofmultiple sclerosis reduced the severity of the disease. Thiswas related to the inhibition of pathogenic T-cell proliferation and to reduced pro-inflammatory cytokine secretion in the lymph nodes of ISLAD-treated EAE mice. The data suggest that T-cell inactivation by HIV during membrane fusion may lie in part in this conserved sequence associated with the gp41 loop region.

Original languageEnglish
Pages (from-to)2244-2252
Number of pages9
JournalBlood
Volume121
Issue number12
DOIs
StatePublished - 2013
Externally publishedYes

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