Interleukin-15 receptor subunit beta – Interleukin-2 receptor subunit gamma heterodimer (IL-15Rβ/γc)

The Interleukin-15 receptor subunit beta – Interleukin-2 receptor subunit gamma heterodimer is a signaling complex essential for the biological activity of Interleukin-15 (IL-15) and Interleukin-2 (IL-2) (UniProt P14784; UniProt P31785). While IL-15 binds with high affinity to the IL-15 receptor alpha (IL-15Rα) subunit, the actual signal transduction occurs through the recruitment of the IL-15Rβ (CD122) and the common gamma chain (γc, CD132) subunits (Waldmann, T. A., 2015). Upon formation of the β/γc heterodimer, the Janus kinase (JAK) 1 and 3 pathways are activated, leading to the phosphorylation of STAT5 and subsequent gene transcription (Robinson, T. O., & Schluns, K. S., 2017). This process is vital for the proliferation, survival, and effector function of Natural Killer (NK) cells and memory CD8+ T cells, which are key components of the anti-tumor immune response. Consequently, this heterodimer is a major target for IL-15 superagonists and modified IL-2 therapies designed to stimulate the immune system in patients with various cancers (Chamie, K., et al., 2022). Therapeutic challenges include managing potential cytokine release syndrome and ensuring selectivity to avoid the activation of regulatory T cells, which can suppress the desired immune response.

Other names

CD122/CD132 heterodimerIL-15Rβ/γcIL-2Rβ/γcInterleukin-15 receptor beta/gamma complexCommon gamma chain-CD122 complex

Agonism of the IL-15Rβ/γc complex to stimulate the proliferation and activation of CD8+ T cells and Natural Killer (NK) cells for oncology applications.