– The IL12 receptor complex, formed by IL12RB1 and IL12RB2, mediates the type I immune responses of various types of lymphocytes. Its ligand, IL12, is a heterodimeric cytokine composed of IL-12p35 and IL-12p40 subunits that are linked via disulfide bonds. Ligation of IL-12 to its receptor involves the binding of IL-12p35 to IL12RB1 and IL-12p40 to IL12RB2. This will result in the activation of tyrosine kinase 2 (TYK2), which is associated with the IL12RB1 chain and Janus kinase 2 (JAK2), which is associated with the IL12RB2 chain. Activated TYK2 and JAK2 direct the phosphorylation of STAT4. IL12RB1 is present on all lymphocytes, while the expression of IL12RB2 is tightly regulated. It has shown that the expression of IL12RB2 is limited to Th2 cells. IL12RB2 subunit plays an important role in Th1 cell differentiation, since its absence leads to an abortive Th1 differentiation that has dysfunctional production of Th1 effector molecules.