Multichain structure of the IFN-α receptor on hematopoietic cells

The structure of IFN-α receptor was studied by 1) developing antibodies against the receptor, and 2) screening a number of cell lines by affinity cross-linking to identify cells that express different IFN-α2 receptor structures. We report that two different patterns of IFN-α2 receptor are observed in human cells of hematopoietic origin. The predominant form of the IFN-α receptor is a multichain structure in which IFN-α2 forms complexes of 110 and 130 kDa (α-subunit). A high M(r) complex of 210 kDa results from the association of α-subunit and other receptor components. In contrast, another form of the receptor has been identified in the IFN-α-resistant U-937 cell line and in some cases of acute leukemia. This form of the IFN-α receptor is characterized by the presence of the α- subunit, and the absence of the 110- and 210-kDa bands. Also a novel 180-kDa complex and a more prominent 75-kDa band are observed. Functional studies performed in U-937 cells showed that this cell line is not only partially resistant to the antiproliferative and antiviral effects of IFN-α, but also fails to down-regulate the α-subunit of the IFN-α receptor upon IFN-α binding.