3 DISTINCT LOCI ON HUMAN-CHROMOSOME-21 CONTRIBUTE TO INTERFERON-ALPHABETA RESPONSIVENESS/

The species specificity of inteferons (IFNs) depends on restricted rec ognition of these ligands by multisubunit cell surface receptors. Expr ession of the human receptor subunit IFNAR In mouse cells conferred se nsitivity only to one subtype of human IFN, IFN-alpha B. Other genes o n human chromosome 21 were required for responses to other subtypes of type I IFN. In contrast IFNAR expression in hamster cells did not con fer sensitivity to any human IFN tested, including IFN-alpha B. Using human-hamster somatic cell hybrids, we mapped the Ifnabr gene, encodin g a ligand-binding subunit of the IFN-alpha/beta (type I) receptor; to human chromosome 21. Ifnabr colocalized with Ifnar to the distal regi on of q22.1. The presence of a chromosomal fragment encoding IFNABR an d IFNAR was also not sufficient to confer sensitivity to human IFN. In contrast hybrids carrying in addition the region 21q22.2 showed a ful l response to human IFN-alpha B, suggesting that a gene located in thi s region encodes a third factor required for type I IFN receptor activ ity.