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

The Interleukin-2 receptor beta/gamma (IL-2Rβ/γc) complex is the primary signaling unit for both Interleukin-2 (IL-2) and Interleukin-15 (IL-15) cytokines (UniProt: P14784, P31785). It consists of the IL-2 receptor subunit beta (CD122) and the common cytokine receptor gamma chain (CD132) (Waldmann, T. A., 2015). While IL-15 signaling often involves a high-affinity alpha subunit (IL-15Rα) for trans-presentation, the β/γc heterodimer is responsible for initiating intracellular cascades, primarily the JAK/STAT pathway (JAK1/JAK3 and STAT5) (Robinson, T. O., & Schluns, K. S., 2017). This signaling is vital for the development, survival, and activation of cytotoxic immune cells, including Natural Killer (NK) cells and memory CD8+ T cells. In therapeutic contexts, this complex is targeted by engineered IL-2 or IL-15 agonists to stimulate anti-tumor immunity while minimizing the activation of regulatory T cells (Tregs) and reducing toxicities like vascular leak syndrome, which are often associated with the IL-2 receptor alpha subunit (CD25) (FDA, 2024). Consequently, the IL-2Rβ/γc complex is a focal point for developing immunotherapies against various cancers and chronic infections.

Other names

CD122/CD132 complexIL-2RβγIL-15RβγInterleukin-15 receptor signaling complexIL-2 receptor beta/gamma heterodimer

Agonism of the IL-2Rβ/γc heterodimer to activate the JAK/STAT signaling pathway, specifically involving JAK1, JAK3, and STAT5, which promotes the survival and expansion of CD8+ effector T cells and Natural Killer (NK) cells (Waldmann, T. A., 2015; Robinson, T. O., & Schluns, K. S., 2017).