Interleukin 12 (IL-12), the founding member of the IL-12 family of heterodimeric cytokines, is composed of two disulfide-linked 35 kDa and 40 kDa subunits. The 35 kDa subunit (p35) is a alpha -helical protein homologous to IL-6 and G-CSF. The 40 kDa subunit (p40) contains one fibronectin type III and one Ig C2-like domain, and has a high degree of structural homology to type I cytokine receptors. Whereas p35 subunit is unique to IL-12, the p40 subunit is also a subunit of IL-23. IL-12 is an essential mediator of cellular-immunity that induces T cells and natural-killer cells to produce IFN-gamma. It is also required for the expansion and activation Th1 cells (1, 2).
The biological activities of IL-12 are mediated through the high-affinity receptor complex composed of the IL-12 Receptor beta 1 (IL-12 R beta 1) and IL-12 Receptor beta 2 (IL‑12 R beta 2) subunits. IL-12 R beta 1 is a 100 kDa protein that is also a subunit of the IL-23 receptor complex. It binds IL-12/IL-23 p40 and is associated with Tyk2. IL-12 R beta 2 is a 130 kDa protein that interacts with p35 and is associated with Jak2. Both receptor subunits are type I membrane proteins that share similarities with the gp130/G-CSF R subgroup in the cytokine receptor superfamily. IL-12 R beta 2 cDNA encodes a 862 amino acid (aa) residue protein with a putative 27 aa residue signal peptide that is cleaved to generate the mature protein with a 595 aa residue extracellular domain, a 24 aa residue transmembrane domain and a 216 aa residue cytoplasmic region. Human and mouse IL-12 R beta 2 share 68% amino acid sequence identity. Whereas IL-12 R beta 1 expression has been detected in activated T cells, NK cells and B cells, the expression of IL-12 R beta 2 is more restricted. Among T cells, IL-12 R beta 2 is absent on naive T cells. Activation of T cells via TCR up‑regulates IL‑12 R beta 2 expression on human Th1 but not Th2 cells (1‑4).
