IL?18 R alpha by itself binds IL-18 with low-affinity and IL-18 R beta does not bind IL-18 in vitro, co-expression of IL-18 R alpha and IL-18 R beta is required for high-affinity binding and IL-18 responsiveness. Human IL-18 R beta cDNA encodes a 599 amino acid (aa) residue precursor type I membrane protein with a 14 aa signal peptide, a 342 aa extracellular region containing three immunoglobulin-like domains, a single transmembrane domain and a 222 aa cytoplasmic domain. Human and mouse IL-18 R beta share 65% aa sequence identity. The expression of IL-18 R beta parallels that of IL-18 R alpha and is detected in numerous tissues including lung, spleen, leukocytes and colon.