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

The Interleukin-2 receptor subunit beta and subunit gamma heterodimer (IL-2Rβγ) is a transmembrane protein complex that serves as the intermediate-affinity receptor for the cytokine Interleukin-2 (IL-2). It is composed of the IL-2 receptor beta subunit (CD122) and the common cytokine receptor gamma chain (CD132), which is shared among several interleukin receptors (Source: UniProt P14784, P31785). This heterodimer is primarily expressed on the surface of resting memory CD8+ T cells and Natural Killer (NK) cells, where its activation triggers the JAK/STAT signaling pathway to promote cell survival and proliferation (Source: PubMed PMID: 22391954). In contrast to the high-affinity trimeric receptor that includes CD25, the IL-2Rβγ heterodimer is a major focus in cancer immunotherapy because it allows for the stimulation of cytotoxic effector cells without the simultaneous activation of immunosuppressive regulatory T cells (Source: StatPearls, Interleukin-2). Therapeutic agents such as engineered IL-2 variants and biased agonists are designed to selectively bind this heterodimer to enhance anti-tumor immune responses while minimizing systemic toxicities like vascular leak syndrome (Source: Journal for ImmunoTherapy of Cancer). These drugs are currently being investigated for the treatment of various advanced malignancies, including metastatic melanoma and renal cell carcinoma (Source: ClinicalTrials.gov).

Other names

Intermediate-affinity IL-2 receptorCD122/CD132 complexIL-2R beta/gammaIL-2Rβ/γcNon-alpha IL-2 receptor

Selective agonism of the IL-2Rβγ complex to promote the expansion of CD8+ effector T cells and Natural Killer cells without preferentially activating regulatory T cells (Source: PubMed PMID: 31015318).