A GENE ON HUMAN-CHROMOSOME-21 LOCATED IN THE REGION 21Q22.2 TO 21Q22.3 ENCODES A FACTOR NECESSARY FOR SIGNAL-TRANSDUCTION AND ANTIVIRAL RESPONSE TO TYPE-I INTERFERONS

The type I interferons (IFNs) are a family of multifunctional cytokine s which includes the 15 IFN alpha subtypes and IFN beta. These IFNs co mpete for binding to cell surface receptors. However, murine cells tra nsfected with a cDNA for a human IFN alpha receptor (IFNAR) developed an antiviral response only to human IFN alpha B, but not to human IFN alpha 2 nor -beta(1). In this study we show, using a panel of CHO huma n chromosome 21 hybrid cell lines which all express IFNAR, that only t hose containing the region 21q22.2 to 21q22.3 transduce signals for IF N responses. Two such hybrid cell lines responded to IFNs alpha 2, -al pha B and -beta by induction of 2'-5' oligoadenylate synthetase and re sistance to viral infection. Other hybrid cell lines, that lacked the region 21q22.2-3, failed to transduce signals as above; even though th ey expressed IFNAR and bound human IFN alpha 2, -alpha B, and -beta. T hese data demonstrate that a gene(s) located in the region 21q22.2-3 e ncodes a factor(s) which is necessary for signaling but does not influ ence ligand binding. This factor is not the cofactor required for IFN gamma signaling which is located in the region 21p to 21q22.1(2).