Expression of a functional human Type I interferon receptor in hamster cells: Application of functional yeast artificial chromosome (YAC) screening

The previously cloned human interferon α/β (Hu-IFN-α/β; Type I interferon) receptor cDNA appears to be only one component of a receptor complex since expression of the cDNA in mouse cells confers sensitivity only to Hu-IFN-αB2, but a monoclonal antibody against this cloned receptor subunit inhibits biological activities of Hu-IFN-αA, Hu-IFN-αB2, Hu-IFN- ω, and Hu-IFN-β. Here we report that a yeast artificial chromosome (YAC) containing a segment of human chromosome 21 introduced into Chinese hamster ovary (CHO) cells confers upon these cells a greatly enhanced response to Hu- IFN-αA and Hu-IFN-αB2 as well as an increased response to Hu-IFN-ω, Hu- IFN-αA/D (Bgl), and Hu-IFN-β. These responses were measured by induction of class I MHC antigens and by protection against encephalomyocarditis virus and vesicular stomatitis virus. Furthermore, these cells exhibit specific high affinity binding of Hu-IFN-αA and Hu-IFN-αB2, Hu-IFN-β, and Hu-IFN-ω. The results indicate that all the genes necessary to reconstitute a biologically active Type I human IFN receptor complex are located within the human DNA insert of this YAC clone.