T-cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15.
The Ixodes scapularis salivary protein Salp15 inhibits the activation of T cells through its interaction with the coreceptor CD4. Salp15 prevents the activation of Lck upon TCR engagement and the formation of lipid rafts. We have now analyzed the signaling pathways that are inhibited by the tick salivary protein in CD4(+) T cells. Salp15 affects tyrosine phosphorylation of several early signal components downstream of Lck, including LAT and Vav1, which results in improper actin polymerization. The effect of Salp15 is due to its interaction with CD4, as no effect was observed in CD4-negative T cells. Finally, we demonstrate that the peptide that mediates the interaction of Salp15 with CD4, P11, is able to recapitulate the immunosuppressive activity of the whole protein. These results clarify the molecular mechanisms of action of Salp15 on T cells and suggest that binding to CD4 is sufficient to elicit its immunosuppressive effect.
Juncadella
Ignacio J
IJ
Department of Veterinary and Animal Sciences, University of Massachussets Amherst, Amherst, MA 01003, USA.
Garg
Renu
R
Ananthnarayanan
Shobana K
SK
Yengo
Christopher M
CM
Anguita
Juan
J
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018884:Ixodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D012463:Saliva / Q000276:immunology; D012471:Salivary Proteins and Peptides / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010455:Peptides; D010750:Phosphoproteins; D051567:Proto-Oncogene Proteins c-vav; D012471:Salivary Proteins and Peptides; C464566:Salp15 protein, Ixodes scapularis; C496619:Vav1 protein, mouse