The high‑affinity IL‑12 receptor complex includes the 100 kDa IL‑12 receptor beta 1 (IL‑12 R beta 1) and the 130 kDa IL‑12 Receptor  beta 2 (IL‑12 R beta 2) subunits, both of which are type I transmembrane proteins that belong to the cytokine receptor superfamily (1, 2). The complexs 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 beta 2 binds IL‑12 alpha and signals through Jak2, while IL‑12 R beta 1 binds IL‑12 beta and signals through Tyk2 (3).
IL‑12 R beta 1 is also a subunit of the IL‑23 receptor complex (3). The 874 amino acid (aa) mouse IL‑12 R beta 2 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 beta 2 ECD shares 91% aa sequence identity with rat IL‑12 R beta 2, and 68% with human, porcine and bovine IL‑12 R beta 2. Human and mouse IL‑12 R beta 2 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 beta 1, which is constitutively expressed on T cells, NK cells and B cells, IL‑12 R beta 2 expression is more restricted (2). On naïve T cells, IL‑12 R beta 2 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 beta 2 causes systemic overexpression 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 beta 2 gene is associated with systemic sclerosis (11).

1. Presky, D.H. et al. (1996) Proc. Natl. Acad. Sci. USA 93:14002.
2. Pistoia, V. et al. (2009) J. Clin. Oncol. 27:4809.
3. Zou, J. et al. (1997) J. Biol. Chem. 272:6073.
4. GenBank protein Accession # P97378.
5. Rogge, L. et al. (1997) J. Exp. Med. 185:825.
6. Becskei, A. and M.J. Grusby (2007) FEBS Lett. 581:5199.
7. Szabo, S.J. et al. (1997) J. Exp. Med. 185:817.
8. Zhao, Z. et al. (2008) J. Immunol. 181:3870.
9. Gran, B. et al. (2010) Exp. Mol. Pathol. 89:126.
10. Airoldi, I. et al. (2005) Blood 106:3846.
11. Bossini-Castillo, L. et al. (2011) Hum. Mol. Genet. Nov. 29 [Epub ahead of print].