Interleukin-15 receptor subunit beta (IL2RB (also known as CD122))

The Interleukin-15 receptor subunit beta (IL2RB, also known as CD122) is a shared signaling component of the IL-15 and IL-2 receptor complexes, forming a heterodimer with the common gamma chain (γc/CD132) to transduce signals critical for T cell and natural killer (NK) cell proliferation, survival, and function. IL-15 binds this beta-gamma complex with intermediate affinity, but IL-15Rα enhances potency through trans-presentation and allosteric stabilization, increasing IL2RB affinity over 100-fold and enabling effective immune activation despite lower intrinsic binding compared to IL-2. Structurally, IL2RB features sushi domains and induces nearly identical receptor geometries in IL-15 and IL-2 quaternary complexes, activating JAK1/STAT5 pathways that promote anti-microbial and anti-tumor responses. In disease, IL2RB signaling drives protective immunity against infections and tumors but contributes to inflammation and autoimmunity when dysregulated. Therapeutically, IL2RB is targeted by IL-15 superagonists like nogapendekin alfa inbakicept and nanrilkefusp alfa, which mimic trans-presentation for enhanced NK and CD8+ T cell activity in cancer immunotherapy, though challenges include managing excessive immune activation.

Other names

IL-2 receptor beta subunitIL-2RβCD122interleukin 2 receptor subunit beta

Receptor heterodimerization with gamma chain (γc/CD132) upon IL-15 binding, activation of JAK1 (via beta chain) and JAK3 (via gamma chain), phosphorylation of STAT3 and STAT5 leading to downstream signaling for lymphocyte proliferation and survival; trans-presentation enhanced by IL-15Rα allostery increasing affinity for IL2RB