title: HIV-1 gp41 and TCRalpha trans-membrane domains share a motif exploited by the HIV virus to modulate T-cell proliferation.
abstract: Viruses have evolved several strategies to modify cellular processes and evade the immune response in order to successfully infect, replicate, and persist in the host. By utilizing in-silico testing of a transmembrane sequence library derived from virus protein sequences, we have pin-pointed a nine amino-acid motif shared by a group of different viruses; this motif resembles the transmembrane domain of the alpha-subunit of the T-cell receptor (TCRalpha). The most striking similarity was found within the immunodeficiency virus (SIV and HIV) glycoprotein 41 TMD (gp41 TMD). Previous studies have shown that stable interactions between TCRalpha and CD3 are localized to this nine amino acid motif within TCRalpha, and a peptide derived from it (TCRalpha TMD, GLRILLLKV) interfered and intervened in the TCR function when added exogenously. We now report that the gp41 TMD peptide co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the TCRalpha TMD and also from the other two known immunosuppressive regions within gp41.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Cohen
authors.forename: Shmuel Jaffe
authors.initials: SJ
authors.lastname: Cohen
authors.forename: Niv
authors.initials: N
authors.lastname: Antonovsky
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D019295:Computational Biology; D004735:Energy Transfer; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D015700:HIV Envelope Protein gp41; D007476:Ionophores; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C514787:gp41 protein, Human immunodeficiency virus 1; D015759:Ionomycin
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