title: Cutting edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15.
abstract: Salp15 is an Ixodes scapularis salivary protein that inhibits CD4+ T cell activation through the repression of TCR ligation-triggered calcium fluxes and IL-2 production. We show in this study that Salp15 binds specifically to the CD4 coreceptor on mammalian host T cells. Salp15 specifically associates through its C-terminal residues with the outermost two extracellular domains of CD4. Upon binding to CD4, Salp15 inhibits the subsequent TCR ligation-induced T cell signaling at the earliest steps including tyrosine phosphorylation of the Src kinase Lck, downstream effector proteins, and lipid raft reorganization. These results provide a molecular basis to understanding the immunosuppressive activity of Salp15 and its specificity for CD4+ T cells.
authors.affiliation: Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: Garg
authors.forename: Ignacio J
authors.initials: IJ
authors.lastname: Juncadella
authors.forename: Nandhini
authors.initials: N
authors.lastname: Ramamoorthi
authors.lastname: Ashish
authors.forename: Shobana K
authors.initials: SK
authors.lastname: Ananthanarayanan
authors.forename: Venetta
authors.initials: V
authors.lastname: Thomas
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincón
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Krueger
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Yengo
authors.forename: Juan
authors.initials: J
authors.lastname: Anguita
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D018884:Ixodes / Q000276:immunology* / Q000378:metabolism*; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D012471:Salivary Proteins and Peptides / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D012471:Salivary Proteins and Peptides; C464566:Salp15 protein, Ixodes scapularis