Intermediate-affinity interleukin-2 receptor (IL-2Rβγ) (IL-2Rβγ)

The intermediate-affinity interleukin-2 receptor (IL-2Rβγ) is a heterodimeric protein complex consisting of the IL-2 receptor subunit beta (CD122) and the common gamma chain (CD132) (UniProt, 2024). It is primarily expressed on the surface of resting CD8+ cytotoxic T cells and natural killer (NK) cells, where it mediates essential signals for cell survival and proliferation (PubMed, PMID: 22391954). Upon binding with interleukin-2 (IL-2), the receptor triggers the JAK/STAT signaling pathway, predominantly leading to the phosphorylation of STAT5 (StatPearls, 2023). In cancer therapy, this receptor is targeted by engineered IL-2 variants, such as bempegaldesleukin and nemvaleukin alfa, which are designed to selectively activate effector cells while avoiding the high-affinity trimeric receptor (containing CD25) found on immunosuppressive regulatory T cells (Tregs) (Journal for ImmunoTherapy of Cancer, 2021). This selective agonism aims to maximize anti-tumor activity and improve the safety profile by reducing the risk of vascular leak syndrome associated with CD25 binding on endothelial cells (Nature Reviews Drug Discovery, 2022).

Other names

CD122/CD132 complexDimeric interleukin-2 receptorIL-2 receptor subunit beta/gamma complexIL-2Rβγc

Selective agonism of the IL-2Rβγ complex to promote the expansion and activation of effector CD8+ T cells and natural killer (NK) cells while minimizing the stimulation of regulatory T cells (Tregs) and vascular endothelial cells.