Cutting edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15.
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.
Garg
Renu
R
Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Juncadella
Ignacio J
IJ
Ramamoorthi
Nandhini
N
Ashish
Ananthanarayanan
Shobana K
SK
Thomas
Venetta
V
Rincón
Mercedes
M
Krueger
Joanna K
JK
Fikrig
Erol
E
Yengo
Christopher M
CM
Anguita
Juan
J
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
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