IDENTIFICATION OF A NOVEL SUBUNIT OF THE TYPE-I INTERFERON RECEPTOR LOCALIZED TO HUMAN CHROMOSOME-21

Expression in mouse cells of the cloned human IFN alpha receptor (IFNa lphaR) subunit selectively confers response and binding to human IFNal pha8, indicating that other subunits are involved in IFNalpha binding. We report here that a new monoclonal antibody (mAb), termed IFNaRbeta 1, recognizes a novel IFNalphaR subunit different from the one recentl y cloned and distinct from the alpha subunit recognized by the IFNalph aR3 mAb. The IFNaRbeta1 mAb blocks the biological effect of seven diff erent Type I IFNs. Immunoprecipitations after cell surface iodination demonstrate that the IFNaRbeta1 mAb recognizes a protein with a molecu lar mass of 100 kDa in Daudi and U-266 cells that express normal IFNal phaR. However, a 55-kDa protein instead of the 100-kDa product was imm unoprecipitated in the IFNalpha-resistant U-937 cell line that express the variant form of the receptor. We also demonstrate that the gene t hat codes for this novel IFNalphaR subunit maps to human chromosome 21 , as do the cloned IFNalphaR subunit and the alpha subunit, indicating the existence of a locus on this chromosome that regulates binding fo r Type I IFNs.