Mammalian type I interferon receptors consists of two subunits: IFNaR1 and IFNaR2

The human type I interferon (IFN) receptor consists of two essential subunits, huIFNaR1 and huIFNaR2; however, so far only IFNaR1 has been identified in other species. Furthermore, it has been suggested that in some species the type I IFN receptor may consist of a single subunit, since expression of murine IFNaR1 in human cells rendered them responsive to several type I murine IFNs. To resolve this issue, we screened a mouse cDNA library with a probe derived from huIFNaR2 cDNA. A cDNA clone, coding for a transmembrane protein which has 49% identity with huIFNaR2 was isolated. This level of identity suggests that this cDNA codes for a muIFNaR2. In addition, several cDNA clones, coding for two distinct soluble variants of muIFNaR2 were identified. To test whether muIFNaR2 is a functional component of the receptor, we co-expressed it with muIFNaR1 in human cells and with an IFN-responsive luciferase reporter vector. Treatment of these cells with muIFN-beta induced high levels of luciferase, whereas no induction was obtained in cells expressing only one of the two subunits. We therefore conclude that the murine type I IFN receptor consists of two different subunits--a configuration shared by humans, and probably all other mammals.