Abstract
Agents that are able to neutralize the activity of IFNγ may have a potential application in the control of alloreactions and organ transplantations or in the therapy of autoimmune disorders, chronic inflammations, septic shocks, multiple sclerosis or delayed hypersensitivities. The discovery of such antagonistic drugs needs the engineering of a soluble form of IFNγ receptor to be used in a cell free receptor binding assay for screening natural or synthetic compounds, which inhibit IFNγ binding. The monoclonal antibodies that inhibit the binding of IFNγ, recognize two different conformational epitopes and indicate that the N-terminal end of the receptor is extracellular while its C terminus is intracellular. Based on the mapping of these functional extracellular epitopes, we express the extracellular domain of this receptor in E. coli. We obtained a soluble protein (P41H6) that bind IFNγ with an affinity which is 10-fold lower as compared to the native membrane-bound receptor. This soluble IFNγ receptor has been used to develop a solid phase binding assay for high-flux screening of IFNγ antagonists.
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Ozmen, L., Fountoulakis, M., Stüber, D., Garotta, G. (1990). The IFNγ Receptor as Tool for the Discovery of New Immunomodulatory Drugs. In: Crommelin, D.J.A., Schellekens, H. (eds) From Clone to Clinic. Developments in Biotherapy, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3780-5_35
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DOI: https://doi.org/10.1007/978-94-011-3780-5_35
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