Interleukin-2 receptor subunit beta (CD122) (IL-2Rβ)

The Interleukin-2 receptor (IL-2R) on effector CD8+ T cells and natural killer (NK) cells is a dimeric protein complex primarily composed of the Interleukin-2 receptor subunit beta (CD122) and the common gamma chain (CD132) [UniProt P14784, P31785]. This intermediate-affinity receptor is distinct from the high-affinity trimeric receptor (which includes the CD25 alpha subunit) found on regulatory T cells (Tregs), making it a critical target for selective immune activation [Nature Reviews Immunology, 2012]. Binding of IL-2 or its engineered analogs to the beta-gamma complex triggers the JAK1/JAK3 and STAT5 signaling pathways, which drive the expansion and cytotoxic maturation of CD8+ T cells and NK cells to eliminate tumor cells [PubMed: 29902506]. In clinical oncology, drug development focuses on "not-alpha" IL-2 variants that preferentially bind to CD122/CD132 to promote anti-tumor immunity while avoiding the immunosuppressive effects of Treg stimulation and reducing the risk of vascular leak syndrome associated with CD25 binding [Journal for ImmunoTherapy of Cancer, 2021]. These agents, such as Nemvaleukin alfa and MDNA11, are currently being investigated to enhance the efficacy of checkpoint inhibitors in various solid tumors [ClinicalTrials.gov].

Other names

CD122IL2RBP70-75Interleukin-2 receptor beta chainInterleukin-2 receptor subunit betaIL-2 receptor on effector CD8+ T cells and NK cells

Agonism of the intermediate-affinity IL-2 receptor complex (IL-2Rβγ) to stimulate effector T cell and NK cell proliferation and activity.