Interleukin-2 receptor subunit beta (IL-2RB) (IL-2RB)

Interleukin-2 receptor subunit beta (IL-2RB), also known as CD122, is a type I transmembrane protein that serves as a shared signaling component for both the IL-2 and IL-15 receptor complexes (UniProt P14784). It associates with the common cytokine receptor gamma chain (CD132) to form a heterodimeric receptor that transmits signals via the Janus kinase (JAK) 1 and 3 and Signal Transducer and Activator of Transcription (STAT) 5 pathways (PubMed: 29902446). This signaling is vital for the development, activation, and proliferation of effector immune cells, including CD8+ T cells and natural killer (NK) cells (PubMed: 24076480). In oncology, IL-2RB is targeted by engineered cytokine variants, such as Bempegaldesleukin and Nemvaleukin alfa, which are designed to selectively bind IL-2RB/gamma over the high-affinity IL-2R alpha (CD25) to promote anti-tumor immunity while minimizing the activation of regulatory T cells (PubMed: 31511301). Beyond cancer, IL-2RB is implicated in autoimmune diseases like vitiligo and alopecia areata, where its signaling contributes to the maintenance of autoreactive T cells, making it a target for antagonistic therapies (PubMed: 30021119). Therapeutic challenges include managing systemic toxicities like vascular leak syndrome and cytokine release syndrome, which result from potent immune activation (PubMed: 31073076). Additionally, the development of IL-2RB-biased agonists aims to improve the therapeutic window of cytokine therapy by reducing off-target effects associated with CD25 binding on endothelial cells (PubMed: 22446627). Monitoring biomarkers such as STAT5 phosphorylation and peripheral immune cell expansion is crucial for assessing the efficacy of drugs targeting this receptor (PubMed: 31511301).

Other names

CD122IL-15 receptor subunit betaIL-15RBP75Interleukin-2 receptor subunit betaInterleukin-15 receptor subunit beta

Agonism of the IL-2/IL-15 receptor beta-gamma complex to stimulate effector T-cell and NK-cell activity; Antagonism to inhibit immune-mediated inflammation.