Interleukin-2 receptor subunit beta and common subunit gamma (IL-2Rβγ)

The interleukin-2 receptor beta-gamma (IL-2Rβγ) complex is a heterodimeric cytokine receptor composed of the IL-2 receptor subunit beta (CD122) and the common cytokine receptor gamma chain (CD132) [UniProt: P14784, P31785]. It serves as the intermediate-affinity receptor for interleukin-2 (IL-2) and is predominantly expressed on memory CD8+ T cells and natural killer (NK) cells [PMID: 22391154]. Unlike the high-affinity trimeric receptor (IL-2Rαβγ) found on regulatory T cells (Tregs), the βγ complex does not require the alpha subunit (CD25) for signaling [PMID: 31004049]. In oncology, this receptor is a critical therapeutic target for next-generation IL-2 therapies, such as bempegaldesleukin and nemvaleukin alfa, designed to selectively activate tumor-killing effector cells while minimizing the expansion of immunosuppressive Tregs [PMID: 33106617]. By signaling through the JAK/STAT pathway, primarily STAT5, activation of IL-2Rβγ promotes the proliferation and cytolytic activity of immune cells against malignancies [PMID: 24075970]. However, therapeutic challenges include managing systemic toxicities like vascular leak syndrome and ensuring sufficient selectivity to avoid off-target effects associated with high-dose IL-2 therapy [PMID: 29109440].

Other names

CD122/CD132 complexIntermediate-affinity interleukin-2 receptorIL-2R beta-gammaIL-2RβγCD122-CD132 heterodimer

Selective agonism of the intermediate-affinity IL-2 receptor complex to stimulate effector CD8+ T cells and NK cells while bypassing the high-affinity IL-2Rα (CD25) subunit to limit regulatory T cell expansion.