Interleukin-2 receptor subunit beta and cytokine receptor common subunit gamma complex (IL-2Rβ/γc)

The Interleukin-2 receptor subunit beta (IL-2Rβ, CD122) and the common cytokine receptor gamma chain (γc, CD132) form the signaling heterodimer of the Interleukin-15 (IL-15) receptor complex (Waldmann, 2015, PubMed: 26407134). This complex is primarily activated on natural killer (NK) cells and CD8+ T cells through the trans-presentation of IL-15 by the IL-15 receptor alpha (IL-15Rα) subunit (Cichocki et al., 2020, PubMed: 32814354). In the context of advanced cell therapies, such as induced NK (iNK) cells, membrane-bound IL-15/IL-15Rα constructs are often used to provide persistent, localized stimulation to these receptors, enhancing cell survival and anti-tumor activity (Fate Therapeutics, 2023). Activation of the IL-2Rβ/γc complex triggers the JAK1/JAK3 and STAT5 signaling pathways, which are critical for immune cell proliferation and effector functions (UniProt: P14784, P31785). This target is a major focus in oncology, with IL-15 superagonists like Nogapendekin alfa-inbakicept (Anktiva) designed to selectively stimulate these receptors to treat various cancers (FDA, 2024).

Other names

CD122/CD132 complexIL-15 receptor beta/gammaIL-15RβγIntermediate-affinity IL-15 receptorIL-2 receptor subunit betaCytokine receptor common subunit gamma

Agonism of the IL-2Rβ/γc receptor complex to induce JAK/STAT signaling, promoting NK cell survival, proliferation, and cytotoxicity.