Interleukin-2 receptor subunit beta and gamma complex (IL-2Rβγ)

The Interleukin-2 receptor subunit beta and gamma complex (IL-2Rβγ) is a heterodimeric signaling assembly composed of the IL-2 receptor beta (CD122) and the common gamma chain (CD132). This complex functions as the intermediate-affinity receptor for Interleukin-2 (IL-2) and is predominantly expressed on CD8+ effector T cells and Natural Killer (NK) cells (UniProt P14784, P31785). Upon ligand binding, the complex activates the JAK1/JAK3 and STAT5 signaling pathways, which are essential for the survival, proliferation, and cytolytic activity of these immune cells (PubMed: 31019211). In the context of cancer immunotherapy, the IL-2Rβγ complex is a high-priority target for engineered IL-2 analogs, often referred to as "not-alpha" variants, which are designed to avoid binding to the alpha subunit (CD25). This selectivity is intended to promote robust anti-tumor immunity while preventing the activation of CD25-high regulatory T cells (Tregs), which can suppress the immune response and limit the efficacy of traditional IL-2 therapy (PubMed: 29434354). Furthermore, targeting the βγ complex aims to reduce the risk of vascular leak syndrome, a severe side effect associated with CD25-mediated activation of endothelial cells.

Other names

CD122/CD132 complexIntermediate-affinity interleukin-2 receptorIL-2R beta-gamma heterodimerIL-2 receptor subunit beta/common gamma chain complex

Selective agonism of the intermediate-affinity IL-2 receptor to promote the expansion and activation of CD8+ effector T cells and Natural Killer (NK) cells while minimizing the activation of regulatory T cells (Tregs).