IFNAR2 - Fc Chimera
A DNA sequence encoding the signal peptide and extracellular domain of human IFNAR2 (aa 1-243) was fused to the Fc region of human IgG1 (aa 90-330). The chimeric protein was expressed in modified human 293 cells. Type I interferons (IFN alpha, beta, omega, tau, kappa and zeta) mediate antiviral, antitumor and immunomodulatory functions and these effects are exerted through binding to the type I interferon receptor (IFNR). This receptor is composed of 2 chains, IFNAR1 and IFNAR2. IFNAR2 is a type I membrane protein tyrosine kinase that is widely expressed in different tissues and is a member of the type II cytokine receptor family. In addition to the membrane bound form a soluble form of the IFNAR2 consisting of the extra-cellular ligand binding domain has been described with the ability to act as a Type 1 IFN agonist, by interacting with and activating cellular membrane-bound IFN receptors, or as an Type I IFN antagonist, with the potential for treatment of autoimmune diseases caused by overproduction of Type 1 IFNs. Symansis IFNAR2 is produced as an ECD-Fc fusion protein with the aim of enhancing its activity. ECD-Fc fusion proteins have an advantage over soluble receptors because many receptors are only functional in dimeric form. Fusion to the Fc domain of IgG1 induces dimerization due to the ability of the Fc domain to form disulfide bonds. The resulting dimeric receptor ECD-Fc mimics the activated form of the receptor and possess enhanced affinity for its cognate ligand relative to its monomeric form. For a review on Type I Interferons please refer to Oritani et al., (2001) Cytokine Growth Factor Rev. 12(4): 337-48.