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

The IL-2Rβ/CD122 : γc/CD132 complex, also known as the intermediate-affinity interleukin-2 (IL-2) receptor, is a heterodimeric signaling unit composed of the IL-2 receptor beta subunit and the common cytokine receptor gamma chain [2, 3]. This complex is primarily expressed on natural killer (NK) cells and memory CD8+ T cells, where it mediates the proliferative and cytotoxic effects of IL-2 and IL-15 [2, 6]. Unlike the high-affinity trimeric receptor (which includes the IL-2Rα/CD25 subunit), the βγ heterodimer is the primary driver of effector immune cell activation rather than immunosuppressive regulatory T cell (Treg) expansion [6, 13]. In oncology, therapeutic strategies focus on developing "biased" agonists that selectively target this complex to enhance anti-tumor immunity while minimizing toxicities like vascular leak syndrome associated with CD25 binding [13, 16]. Upon ligand binding, the complex initiates intracellular signaling through the JAK/STAT, PI3K/AKT, and MAPK pathways [9, 14]. This receptor axis is a critical target for next-generation immunotherapies aiming to achieve a better therapeutic index than recombinant IL-2 (aldesleukin) [16, 25]. Beyond cancer, the complex plays a role in maintaining immune homeostasis and is investigated in the context of chronic infections and autoimmune disorders [13, 17]. The heterodimerization of the cytoplasmic domains of IL-2Rβ and γc is essential for the recruitment and activation of JAK1 and JAK3 kinases, respectively [8, 9]. Drugs targeting this complex include engineered IL-2 variants and bispecific antibodies designed to promote the expansion of cytotoxic lymphocytes [16, 25].

Other names

CD122/CD132 complexIntermediate-affinity IL-2 receptorIL-2RβγIL-2R beta/gamma heterodimerIL-15 receptor signaling complex

Agonism of the intermediate-affinity IL-2 receptor to stimulate effector T and NK cells while bypassing the alpha subunit (CD25) to minimize regulatory T cell activation and vascular toxicity [13, 16, 25].