Differential responsiveness of a splice variant of the human type I interferon receptor to interferons

Chinese hamster ovary cells containing the yeast artificial chromosome F136C5 (alpha YAC) respond to all type I human interferons including IFN-alpha A, IFN-beta, and IFN-omega. The alpha YAC contains at least two genes encoding interferon-alpha receptor (IFN-alpha R) chains that are required for response to type I human interferons: Hu-IFN-alpha R1 and Hu-IFN-alpha R2. Ne previously isolated a splice variant of the Hu-IFN-alpha R1 chain designated Hu-IFN-alpha R1s. Chinese hamster ovary cells containing a disrupted alpha YAC, which contains a deletion in the human IFNAR1 gene, were transfected with expression vectors for the Hu IFN-alpha R1 and Hu-IFN-alpha R1s chains, With these cells, two type I interferons have been identified which can interact with the splice valiant (Hu-IFN-alpha R1s) and with the Hu IFN-alpha R1 chains: Hu-IFN-alpha A and IFN-omega. Two other type I interferons, Hu-IFN-alpha B2 and Hu-IFN-alpha F, are capable of signaling through the Hu-IFN-alpha R1 chain only and cannot utilize the splice variant Hu-IFN-alpha R1s. Hu-IFN-alpha R1 and Hu-IFN-alpha R1s differ in that the latter is missing a single subdomain of the receptor extracellular domain encoded by exons 4 and 5 of the IFNAR1 gene. These results therefore indicate that different type I interferons require different subdomains of the Hu-IFN-alpha R1 receptor chain, and that the splice variant chain (Hu-IFN-alpha R1s) is functional.