INTERFERON-GAMMA SIGNALS VIA A HIGH-AFFINITY MULTISUBUNIT RECEPTOR COMPLEX THAT CONTAINS 2 TYPES OF POLYPEPTIDE-CHAIN

Signaling by interferon gamma (lFN-gamma) requires two structurally re lated cell surface proteins: a ligand-binding poly-peptide, known as t he IFN-gamma receptor (IFN-gamma), and an accessory factor, However, i t is not known whether IFN-gamma forms a ternary complex with the IFN- gamma R and accessory fatter to initiate signaling. Here we demonstrat e complex formation between IFN-gamma and the two proteins, both in so lution and at the cell surface. We observe complexes containing ligand , two molecules of IFN-gamma R (designated the IFN-gamma R alpha chain ), and one or two molecules of accessory factor (designated the IFN-ga mma beta chain). Transfected cells expressing both IFN-gamma R chains bind IFN-gamma with higher affinity than do cells expressing cr chain alone. Anti-beta-chain antibodies prevent the beta chain from particip ating in the ligand-receptor complex, reduce the affinity for IFN-gamm a, and block signaling. Soluble alpha- or beta-chain extracellular dom ains also inhibit function. These results demonstrate that IFN-gamma s ignals via a high-affinity multisubunit complex that contains two type s of receptor chain and suggest a potential approach to inhibiting spe cific actions of IFN-gamma by blocking the association of receptor sub units.