The biological activities of IL-12 are mediated through a receptor complex composed of two class I cytokine receptor subunits designated IL-12 R beta 1 and IL-12 R beta 2. Both subunits are required for high-affinity binding and activity of IL-12. IL-12 R beta 1 binds specifically to IL-12 p40, a subunit of the heterodimeric IL-12, and is also a subunit of the IL-23 receptor complex, while IL-12 R beta 2 binds IL-12 p35. IL-12 Rs are predominantly expressed on NK cells and activated T (Th1) cells with some expression also on dendritic cells. Both IL-12 R subunit extracellular domains are composed of three fibronectin-like domains and two cytokine receptor homology domains. IL-12R beta 2 also has an extracellular Ig-like domain.