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牛I型干扰素受体蛋白BoIFNAR-1对人I型干扰素具有高亲和力和广泛特异性。

Bovine type I interferon receptor protein BoIFNAR-1 has high-affinity and broad specificity for human type I interferons.

作者信息

Langer J A, Yang J, Carmillo P, Ling L E

机构信息

Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School-UMDNJ, Piscataway, NJ 08854, USA.

出版信息

FEBS Lett. 1998 Jan 9;421(2):131-5. doi: 10.1016/s0014-5793(97)01550-0.

DOI:10.1016/s0014-5793(97)01550-0
PMID:9468293
Abstract

The type I interferon receptor (IFNAR) is composed of two transmembrane polypeptides, IFNAR-1 and IFNAR-2. Human IFNAR-1 has low intrinsic affinity for IFNs, but enhances the affinity for IFNs of the complex over that of HuIFNAR-2 alone, and modulates the ligand specificity. Bovine cells respond to human alpha interferons. The bovine homologue of HuIFNAR-1, BoIFNAR-1, when expressed in heterologous cells, confers high-affinity binding and broad specificity for human type I IFNs. A soluble fusion protein of the ectodomain of BoIFNAR-1 and an immunoglobulin Fc domain was produced. In contrast to HuIFNAR-1, this protein competes strongly with human cells for IFN binding, and directly binds a wide spectrum of human type I IFNs, including diverse IFN-alphas, IFN-beta and IFN-omega, with moderate to high affinity. This accounts for much of the specificity for human IFNs possessed by bovine cells, with several exceptions. The BoIFNAR-1 ectodomain, in contrast to HuIFNAR-1, may be useful for studies of binary and ternary complexes with IFNs and IFNAR-2, and for purification, assay and biological neutralization protocols.

摘要

I型干扰素受体(IFNAR)由两种跨膜多肽IFNAR-1和IFNAR-2组成。人IFNAR-1对干扰素的内在亲和力较低,但与单独的人IFNAR-2相比,它能增强复合物对干扰素的亲和力,并调节配体特异性。牛细胞对人α干扰素产生反应。人IFNAR-1的牛同源物BoIFNAR-1在异源细胞中表达时,对人I型干扰素具有高亲和力结合和广泛特异性。制备了BoIFNAR-1胞外域与免疫球蛋白Fc结构域的可溶性融合蛋白。与HuIFNAR-1不同,该蛋白在干扰素结合方面与人细胞竞争激烈,并以中度至高亲和力直接结合多种人I型干扰素,包括不同的干扰素α、干扰素β和干扰素ω。这解释了牛细胞对人干扰素具有的大部分特异性,但有几个例外。与HuIFNAR-1不同,BoIFNAR-1胞外域可能有助于研究与干扰素和IFNAR-2的二元和三元复合物,以及用于纯化、检测和生物中和方案。

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