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

The Interleukin-2 receptor subunit beta and Cytokine receptor common subunit gamma (IL-2Rβγ) complex is the primary signaling unit for the cytokines IL-2 and IL-15. This heterodimer consists of CD122 (beta) and CD132 (gamma), which are members of the type I cytokine receptor family (UniProt P14784, P31785). Upon binding its ligand, the complex recruits Janus kinases (JAK1 and JAK3) to trigger downstream signaling through the STAT5, PI3K/AKT, and MAPK pathways. These pathways are critical for driving the expansion and activation of CD8+ T cells and Natural Killer (NK) cells (Liao et al., 2013). Unlike the high-affinity trimeric IL-2 receptor that includes the alpha subunit (CD25), the IL-2Rβγ complex is an intermediate-affinity receptor that is not constitutively expressed on regulatory T cells (Tregs). This distinction makes it a high-value target in oncology, where "biased" agonists like bempegaldesleukin and N-803 are designed to selectively engage the βγ subunits. This strategy aims to enhance anti-tumor immunity while minimizing the immunosuppression and toxicity, such as vascular leak syndrome, associated with CD25 activation (Hurwitz et al., 2021; Chamie et al., 2022). Consequently, the IL-2Rβγ complex is a focal point for developing next-generation cancer treatments and therapies for chronic viral infections.

Other names

CD122/CD132IL-2Rβ/γcIntermediate-affinity IL-2 receptorIL-15 receptor signaling complexP70-75 receptor complex

Selective agonism of the IL-2Rβγ complex to stimulate effector T cell and NK cell proliferation and activation via the JAK/STAT signaling pathway (Liao et al., 2013; Waldmann, 2006).