T-cell inactivation and immunosuppressive activity induced by HIV gp41 via novel interacting motif.
Fusion peptide (FP) of the HIV gp41 molecule inserts into the T cell membrane during virus-cell fusion. FP also blocks the TCR/CD3 interaction needed for antigen-triggered T cell activation. Here we used in vitro (fluorescence and immunoprecipitation), in vivo (T cell mediated autoimmune disease adjuvant arthritis), and in silico methods to identify the FP-TCR novel interaction motif: the alpha-helical transmembrane domain (TMD) of the TCR alpha chain, and the beta-sheet 5-13 region of the 16 N-terminal aa of FP (FP(1-16)). Deciphering the molecular mechanism of the immunosuppressive activity of FP provides a new potential target to overcome the immunosuppressant activity of HIV, and in addition a tool for down-regulating immune mediated inflammation.
Bloch
Itai
I
Department of Biological Chemistry, the Weizmann Institute of Science, Rehovot, 76100 Israel.
Quintana
Francisco J
FJ
Gerber
Doron
D
Cohen
Tomer
T
Cohen
Irun R
IR
Shai
Yechiel
Y
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D031541:Fluorescence Resonance Energy Transfer; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013816:Thermodynamics
D015700:HIV Envelope Protein gp41; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins