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

The Interleukin-2 receptor beta-gamma (IL-2Rβγ) heterodimer is an intermediate-affinity receptor complex composed of the IL-2Rβ (CD122) and the common gamma chain (γc, CD132) subunits (UniProt: P14784, P31785). Unlike the high-affinity trimeric receptor that includes the alpha subunit (CD25), the βγ heterodimer is primarily expressed on resting effector CD8+ T cells and natural killer (NK) cells (Liao et al., Immunity, 2013). Binding of IL-2 to this complex initiates intracellular signaling through the Janus kinase (JAK) 1 and 3 proteins, subsequently activating the STAT5 transcription factor to drive cellular proliferation and effector function (Waldmann, Nature Reviews Immunology, 2006). In oncology, the IL-2Rβγ complex is a major therapeutic target for biased IL-2 formulations, such as Bempegaldesleukin and Nemvaleukin alfa, designed to selectively activate anti-tumor immune cells while bypassing regulatory T cells (Tregs) (Spolski et al., Nature Reviews Immunology, 2018). This selectivity aims to enhance the therapeutic index of IL-2 therapy by reducing systemic toxicity, such as vascular leak syndrome, and avoiding immunosuppressive feedback (Bentebibel et al., Cancer Discovery, 2019).

Other names

Intermediate-affinity interleukin-2 receptorIL-2Rβ/γcCD122/CD132 complexIL-2 receptor subunit beta/gamma heterodimer

Agonism of the intermediate-affinity receptor complex to trigger JAK1/JAK3-mediated STAT5 phosphorylation, leading to the expansion of effector T cells and natural killer cells.