A bivalent immunoadhesin of the human interferon-gamma receptor is an effective inhibitor of IFN-gamma activity.
We describe here the bioengineering of a bivalent IFN-gamma-RFc immunoadhesin consisting of the extracellular domain of the human IFN-gamma receptor alpha chain (IFN-gamma-R) fused to a human IgG1 Fc region (encoding hinge, CH2 and CH3 domain) that was efficiently expressed as a covalently linked homodimer in insect cells and purified in a one-step purification procedure. The IFN-gamma-RFc fusion protein exerted a 3-fold higher ligand binding affinity in binding competition studies in vitro compared with the monovalent extracellular IFN-gamma-R domain. In addition, the in vitro antagonistic activity of IFN-gamma-RFc, as determined by inhibition of IFN-gamma-induced virus protection and HLA-DR expression, was more than 30-fold higher in comparison with the monovalent soluble receptor. The described IFN-gamma-R immunoadhesin is a potential therapeutic reagent to interfere with the disease-promoting activities of IFN-gamma in several autoimmune diseases.
Moosmayer
D
D
Institute of Cell Biology and Immunology, University of Stuttgart, Germany.
Gerlach
E
E
Hauff
R
R
Becker
P
P
Brocks
B
B
Pfizenmaier
K
K
D000818:Animals; D000915:Antibody Affinity; D015703:Antigens, CD / Q000737:chemistry*; D000998:Antiviral Agents / Q000494:pharmacology; D016860:CD4 Immunoadhesins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007313:Insecta; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D017471:Receptors, Interferon / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012995:Solubility; D013045:Species Specificity; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D000998:Antiviral Agents; D016860:CD4 Immunoadhesins; D007371:Interferon-gamma; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D000096743:Interferon gamma Receptor