Interleukin-2 receptor subunit beta (IL-2Rβ) (IL-2Rβ)

Interleukin-2 receptor subunit beta (IL-2Rβ), also known as CD122, is a type I transmembrane glycoprotein that serves as a shared signaling component for the interleukin-2 (IL-2) and interleukin-15 (IL-15) receptors [1, 2]. It forms a medium-affinity heterodimeric receptor when paired with the common cytokine receptor gamma chain (γc) and a high-affinity trimeric receptor when associated with both γc and the IL-2 receptor alpha subunit (CD25) [1]. IL-2Rβ is essential for transmitting signals into the cell, primarily through the activation of Janus kinases (JAK1 and JAK3) and subsequent STAT5 phosphorylation, which drives the proliferation and differentiation of T cells and natural killer (NK) cells [2, 3]. In therapeutic development, IL-2Rβ is a high-priority target for "biased" IL-2 mimetics designed to selectively activate the dimeric IL-2Rβ/γc complex on CD8+ effector T cells and NK cells while avoiding the trimeric CD25-containing receptor on regulatory T cells (Tregs), thereby maximizing anti-tumor activity and minimizing toxicity [3, 4]. Additionally, dysregulation of IL-2Rβ signaling is implicated in various autoimmune conditions and hematologic malignancies, making it a target for both agonistic and antagonistic pharmacological interventions [2, 5].

Other names

CD122IL2RBP70-75Interleukin-2 receptor beta chainInterleukin-15 receptor subunit betaHigh affinity IL-2 receptor subunit beta

Agonism of the IL-2Rβ/γc receptor complex to promote immune effector cell expansion; selective binding to avoid IL-2Rα (CD25) mediated regulatory T cell activation.