Recombinant Mouse IL-12 R beta 2 Fc Chimera Protein, CF

The high‑affinity IL‑12 receptor complex includes the 100 kDa IL‑12 receptor beta1 (IL‑12 R beta1) and the 130 kDa IL‑12 Receptor  beta2 (IL‑12 R beta2) subunits, both of which are type I transmembrane proteins that belong to the cytokine receptor superfamily (1, 2). The complex's ligand, IL‑12, is a disulfide‑linked heterodimer composed of 35 kDa (IL‑12 alpha p35) and 40 kDa (IL‑12 beta p40) subunits. IL‑12 R beta2 binds IL‑12 alpha and signals through Jak2, while IL‑12 R beta1 binds IL‑12 beta and signals through Tyk2 (3). IL‑12 R beta1 is also a subunit of the IL‑23 receptor complex (3). The 874 amino acid (aa) mouse IL‑12 R beta2 precursor includes a 23 aa signal peptide, a 614 aa extracellular domain (ECD), a 21 aa transmembrane segment and a 216 aa cytoplasmic region. The ECD possesses one C2‑type Ig‑like domain, five fibronectin type III (Fn III) repeats, 14 potential N‑glycosylation sites, and a WSXWS motif, while the cytoplasmic region contains a Box 1 motif and three tyrosine phosphorylation sites that presumably mediate intracellular signaling (3). The mouse IL‑12 R beta2 ECD shares 91% aa sequence identity with rat IL‑12 R beta2, and 68% with human, porcine and bovine IL‑12 R beta2. Human and mouse IL‑12 R beta2 do not bind cross‑species IL‑12 (2). A 734 aa mouse isoform that lacks aa 363‑503 within the Fn III domains is reported (4). Unlike IL‑12 R beta1, which is constitutively expressed on T cells, NK cells and B cells, IL‑12 R beta2 expression is more restricted (2). On naïve T cells, IL‑12 R beta2 is expressed following STAT1 activation by IFN‑ gamma, IL‑27 and/or T cell receptor ligation. This up‑regulation allows IL‑12 to promote Th1, but not Th2, differentiation (5‑7). Among B cells, surface expression is limited to naïve germinal center and memory B cells, and myeloma cells (2). Deletion of IL‑12 R beta2 causes systemic over-expression of IL‑6, accelerated maturation of thymocytes, deficient regulatory T cell maturation and function, and reduced splenic T cell apoptosis (2, 8-10). These mice are susceptible to autoimmune diseases such as experimental autoimmune encephalitis and spontaneous B cell malignancies (2, 8-10). In humans, polymorphism of the IL‑12 R beta2 gene is associated with systemic sclerosis (11).