Tick saliva has pleiotropic properties that facilitate persistence of the arthropod upon the host. We now describe a feeding-inducible protein in Ixodes scapularis saliva, Salp15, that inhibits CD4+ T cell activation. The mechanism involves the repression of calcium fluxes triggered by TCR ligation and results in lower production of interleukin-2. Salp15 also inhibits the development of CD4+ T cell-mediated immune responses in vivo, demonstrating the functional importance of this protein. Salp15 provides a molecular basis for understanding the immunosuppressive activity of I. scapularis saliva and vector-host interactions.
