MOLECULAR-CLONING AND CHARACTERIZATION OF A 2ND SUBUNIT OF THE INTERLEUKIN-1 RECEPTOR COMPLEX

A monoclonal antibody (mAb) was isolated that blocked the binding and bioactivity of both human and murine interleukin 1 beta (LI-1 beta) on murine IL-1 receptor-bearing cells. This mAb recognized a protein that was distinct from the Type I and Type II IL-1 receptors, suggesting that an additional protein exists that is involved in IL-1 biological responses. By expression cloning in COS-7 cells, we have isolated a cDNA from mouse 3T3-LI cells encoding this putative auxiliary molecule, which we term the IL-1 receptor accessory protein (IL-1R AcP), Sequence analysis of the cDNA predicts an open reading frame that encodes a 570-amino acid protein with a molecular mass of similar to 66 kDa. The IL-1R AcP is a member of the Ig superfamily by analysis of its putative extracellular domain and also bears limited homology throughout the protein to both Type I and Type II IL-1 receptors, Northern analysis reveals that murine IL-1R AcP mRNA is expressed in many tissues and appears to be regulated by IL-1, In mammalian cells expressing natural or recombinant Type I IL-1R and IL-1R AcP, the accessory protein forms a complex with the Type I IL-1R and either IL-1 alpha or IL-1 beta but not IL-1ra, The recombinant accessory protein also increases the binding affinity of the recombinant Type I HL-1R for IL-1 beta when the two receptor proteins are coexpressed. Therefore, the functional IL-1 receptor appears to be a complex composed of at least two subunits.