Cutrone E C, Langer J A
Department of Molecular Genetics and Microbiology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
FEBS Lett. 1997 Mar 10;404(2-3):197-202. doi: 10.1016/s0014-5793(97)00129-4.
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.
人I型干扰素，包括至少12种α干扰素、β干扰素和ω干扰素，与一种由至少两个跨膜亚基即IFNAR-1和IFNAR-2组成的受体（IFNAR）结合。通过单独测量IFNAR-1或IFNAR-2的结合特性，或共表达时的结合特性，研究了受体亚基对配体结合的作用。IFNAR-1与配体的结合非常弱，但其共表达可提高IFNAR-2对α2干扰素的亲和力。大多数I型干扰素以2 - 20 nM的半数抑制浓度（IC50）单独抑制α2干扰素与IFNAR-2的结合。对于共表达IFNAR-1和IFNAR-2的细胞，相对于单独在IFNAR-2上的值而言，各种配体的IC50值降低了3 - 20倍。因此，虽然IFNAR-2在I型干扰素的亲和力测定和差异识别中起主要作用，但IFNAR-1调节IFNAR-1/IFNAR-2受体复合物的配体亲和力和选择性。
