Interleukin-15 receptor subunit beta and gamma (IL-15Rβγ) (IL-15Rβγ)

The Interleukin-15 receptor beta-gamma (IL-15Rβγ) complex is a heterodimeric signaling receptor composed of the IL-15 receptor subunit beta (CD122) and the common cytokine receptor gamma chain (CD132) [UniProt: P14784, P31785]. Primarily expressed on Natural Killer (NK) cells and memory CD8+ T cells, this complex is responsible for transducing signals that drive the proliferation, survival, and cytotoxic activity of these immune effectors [PMID: 17105822]. Unlike the high-affinity trimeric receptor that includes IL-15Rα, the βγ heterodimer serves as the intermediate-affinity signaling component, often activated via 'trans-presentation' where IL-15 is bound to IL-15Rα on an opposing cell [PMID: 28611164]. In oncology, this receptor is a major therapeutic target for IL-15 agonists and superagonists, such as Nogapendekin alfa inbakicept, which aim to boost anti-tumor immunity while avoiding the regulatory T cell stimulation associated with IL-2 [NCI Drug Dictionary]. Conversely, monoclonal antibodies targeting the CD122 subunit are being investigated for the treatment of autoimmune disorders and T-cell malignancies to inhibit aberrant lymphocyte activation [PMID: 24014551].

Other names

CD122/CD132 complexIL-2/IL-15 receptor beta/gammaInterleukin-15 receptor beta-gamma heterodimerIL-15Rβ/γ

Agonism of the IL-15Rβγ complex to stimulate JAK/STAT signaling and expand NK and memory CD8+ T cells; Antagonism of the CD122 subunit to block IL-15 and IL-2 signaling.