Agents that antagonize the functions of interferon (IFN) are potential pharmaceuticals against several immunological and inflammatory disorders. IFN receptor-immunoglobulin G fusion proteins (IFNR-IgG) function as antagonists of endogenous IFN and have longer half-lives in vivo in comparison with soluble IFN receptors (sIFNR), consisting of the extracellular region of the native sequence. A fusion protein comprising the extracellular domain of the human IFN receptor and the hinge, CH and CH domains of the human IgG3 constant region, was expressed in Chinese hamster ovary cells. The IFNR-IgG3 fusion protein was secreted into the culture medium as a 175-kDa glycoprotein and was purified over Protein G-Sepharose, DEAE-Sepharose, and size exclusion chromatography. IFNR-IgG3 bound IFN in solid phase assays and ligand blots, competed for the binding of radiolabeled IFN to the cell surface receptor of Raji cells, and inhibited the IFN-mediated antiviral activity with an efficiency at least one order of magnitude higher than that of the soluble receptor produced in the same expression system. Two IFNR-IgG3 fusion proteins bound two IFN dimers forming a complex of approximately 380 kDa. In immunodiffusion assays, the IFNR-IgG3 fusion protein did not precipitate IFN. Dissociation of bound IFN from IFNR-IgG3 was 2-fold slower than from the sIFNR produced in insect cells.

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