Contributions of cloned type I interferon receptor subunits to differential ligand binding

The human type I interferons, including at least 12 IFN-alphas, IFN-beta and IFN-omega, bind to a receptor (IFNAR) composed of at least two transmembrane subunits, IFNAR-1 and IFNAR-2. The contributions of the receptor subunits to ligand binding were investigated by measuring the binding properties of IFNAR-1 or IFNAR-2 alone, or when co-expressed. The affinity of IFNAR-2 for IFN-alpha2 was increased by the co-expression of IFNAR-1, which itself binds ligand very weakly. Most type I IFNs inhibited the binding of IFN-alpha2 to IFNAR-2 alone with IC50 values of 2-20 nM. For cells co-expressing IFNAR-1 and IFNAR-2, the IC50 values decreased 3-20-fold for various ligands, relative to their values on IFNAR-2 alone. Thus, while IFNAR-2 plays the major role in affinity determination and differential recognition of type I IFNs, IFNAR-1 modulates both the ligand affinity and selectivity of the IFNAR-1/IFNAR-2 receptor complex.