Three distinct loci on human chromosome 21 contribute to interferon-alpha/beta responsiveness

The species specificity of interferons (IFNs) depends on restricted recognition of these ligands by multisubunit cell surface receptors. Expression of the human receptor subunit IFNAR in mouse cells conferred sensitivity only to one subtype of human IFN, IFN-alpha B. Other genes on human chromosome 21 were required for responses to other subtypes of type I IFN. In contrast, IFNAR expression in hamster cells did not confer sensitivity to any human IFN tested, including IFN-alpha B. Using human-hamster somatic cell hybrids, we mapped the Ifnabr gene, encoding a ligand-binding subunit of the IFN-alpha/beta (type I) receptor, to human chromosome 21. Ifnabr colocalized with Ifnar to the distal region of q22.1. The presence of a chromosomal fragment encoding IFNABR and IFNAR was also not sufficient to confer sensitivity to human IFN. In contrast, hybrids carrying in addition the region 21q22.2 showed a full response to human IFN-alpha B, suggesting that a gene located in this region encodes a third factor required for type I IFN receptor activity.