Interleukin-2 receptor subunit beta and cytokine receptor common subunit gamma complex (IL-15Rβγ) (IL-15Rβγ)

The Interleukin-2 receptor subunit beta and cytokine receptor common subunit gamma complex (IL-15Rβγ) is a heterodimeric cytokine receptor primarily responsible for mediating the effects of Interleukin-15 (IL-15) on effector immune cells (Waldmann, 2015). It consists of the IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain (CD132), which are constitutively expressed on the surface of Natural Killer (NK) cells and memory CD8+ T cells (Robinson & Schluns, 2017). Binding of IL-15 to this complex triggers the JAK1/JAK3 and STAT5 signaling pathways, promoting the survival, proliferation, and enhanced cytotoxic activity of these lymphocytes (Mishra et al., 2014). In cancer therapy, this receptor is a key target for IL-15 agonists and superagonists, which aim to stimulate anti-tumor immunity without the regulatory T cell expansion often induced by IL-2 (Guo et al., 2017). Drugs like nogapendekin alfa inbakicept (N-803) have been developed to exploit this pathway, showing efficacy in treating malignancies such as non-muscle invasive bladder cancer (FDA, 2024). While therapeutically potent, activation of the IL-15Rβγ complex can lead to systemic inflammatory side effects, including cytokine release syndrome and vascular leak syndrome (Waldmann, 2015).

Other names

CD122/CD132 complexIL-2/IL-15 receptor beta/gammaIL-15RB/IL-2RGIntermediate-affinity IL-15 receptorIL-2Rβγ heterodimer

Agonism of the IL-15Rβγ complex to stimulate the proliferation and activation of NK cells and CD8+ effector T cells via the JAK/STAT signaling pathway.