Interleukin-1 receptor accessory protein interacts with the type II interleukin-1 receptor

Stably transfected HEK-293 cells express on their surface the murine type II IL-1 receptor (mIL-1RII) as demonstrated bg FAGS analysis using the mAb 4E2, however binding of [I-125]-hrIL-1 beta to these cells is nearly absent. Saturable high affinity binding of [I-125]-hrIL-1 beta is observed when the murine IL-l receptor accessory protein (mIL-1RAcP) is coexpressed with mIL-1RII. Binding of [125I]-hrIL-1 beta to mIL-1RII-mIL-1RAcP complex can be inhibited either with antibodies to mIL-1RII (mAb 4E2), or by antibodies to mIL-1RAcP (mAb 4C5), The number of high affinity binding sites in cells stably transfected with the cDNA for mIL-1RII is dependent on the dose of cDNA for mIL-1RAcP used to transfect the cells. The high affinity complex between mIL-1RAcP and mIL-1RAcP is not preformed by interaction between the intracellular domains of these two transmembrane proteins, rather it appears to require the extracellular portions of mIL-1RII and mIL-1RAcP and the presence of a ligand, We suggest that in addition to its earlier described decoy receptor role, IL-1RII may modulate the responsiveness of cells to IL-l by binding the IL-1RAcP in unproductive/non-signalling complexes and thus reducing the number of signalling IL-lRI-IL-1RAcP-agonist complexes when IL-1 is bound. (C) 1998 Federation of European Biochemical Societies.