LIGAND-INDUCED ASSOCIATION OF THE TYPE-I INTERFERON RECEPTOR COMPONENTS

Two transmembrane polypeptides, IFNAR and IFN-alpha/beta R, were previ ously identified as essential components of the type I interferon (IFN ) receptor, but their interrelationship and role in ligand binding wer e not clear, To study these issues, we stably expressed and characteri zed the two polypeptides in host murine cells, In human cells, native IFN-alpha/beta R is a 102-kDa protein but upon reduction only a 51-kDa protein is detected, In host murine cells human IFN-alpha/beta R was expressed as a 51-kDa protein, Host cells expressing IFN-alpha/beta R bound IFN-alpha(2) with a high affinity (K-d of 3.6 nM), whereas cells expressing IFNAR exhibited no ligand binding, Upon coexpression of IF NAR and the 51-kDa IFN-alpha/beta R, the affinity for IFN-alpha(2) was increased 10-fold, approaching that of the native receptor. We show b y cross-linking that both the cloned (51-kDa) and native (102-kDa) IFN -alpha/beta R bind IFN-alpha(2) to form an intermediate product, while IFNAR associates with this product to form a ternary complex, Hence, IFNAR and IFN-alpha/beta R are components of a common type I IFN recep tor, cooperating in ligand binding, Ligand-induced association of IFNA R and IFN-alpha/beta R probably triggers transmembrane signaling.