The role of the SD100A domain in IFNAR1 in type I interferon signaling

grantor: University of TorontoThe Type I interferon (IFN) system plays a prevalent role in regulating antiviral and growth inhibitory activities and in modulating the immune system. Study of the signaling pathways associated with these features of the IFN system has led to the observation that IFNs act in a species specific manner and that Type I IFNs are able to signal differentially using the same receptor complex. Furthermore, IFN subtypes require different extracellular receptor domains to elicit signaling. To assess the contribution of the SD100A domain of the IFNAR1 chain to Type I IFN binding and signaling, a chimaeric cDNA construct in which the SD100A domain of the murine chain was replaced with the human equivalent was constructed. This HMM/M IFNAR1 was introduced by transfection into IFNAR1 deficient mouse embryonic fibroblasts and stable transfectants were established for study. Protein extracts from murine IFN-Ã4 treated HMM/M expressing clones and wild-type IFNAR1 (MMM/M) expressing clones show similar Stat activation. Antiviral and antiproliferative responses were also comparable in the MMM/M and HMM/M clones. These results suggest that the IFNAR1 SD100A domain does not contribute to Type I IFN binding and signaling in a species specific manner in the context of murine IFN-Ã4.M.Sc