A CRITICAL ROLE FOR INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN IN INTERLEUKIN-1 SIGNALING

Interleukin-1 (IL-1) is a central molecule in inflammation and immune responses whose pleiotropic activities are mediated by the type I IL-1 receptor (IL-1RI). The IL-1RI alone on the cell surface is silent aft er binding of the ligand. We show that the recently identified IL-1RI accessory protein (IL-1RAcP) converts the silent into a fully function al IL-1RI complex. Although transfection of IL-1RAcP into IL-1RAcP-def icient EL4D6/76 cells did not alter the binding kinetics or dissociati on constants of the I-125-labeled IL-1 alpha/IL-1RI complex, a very ea rly event, internalization of the activated receptor complex, and a la te event, IL-1-stimulated IL-2 production, were successfully restored. Therefore, recruitment of IL-1RAcP is a critical early step in the si gnaling cascade mediated by the IL-1RI activation complex.