Interleukin-2 receptor alpha-beta-gamma complex (IL-2Rαβγ) (IL-2Rαβγ)

The Interleukin-2 receptor alpha-beta-gamma (IL-2Rαβγ) complex is the high-affinity heterotrimeric receptor for interleukin-2 (IL-2), a key cytokine in immune regulation (UniProt: P01589, P14784, P31785). It is composed of three subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and the common gamma chain (γc, CD132). While the dimeric IL-2Rβγ complex has intermediate affinity and is expressed on memory T cells and NK cells, the addition of the α-chain (CD25) increases the binding affinity for IL-2 by approximately 100-fold (Malek, T. R., Annu Rev Immunol, 2008). Regulatory T cells (Tregs) constitutively express high levels of CD25, making them uniquely sensitive to low concentrations of IL-2 that are insufficient to activate effector T cells or NK cells. This selective signaling is essential for the maintenance, survival, and suppressive function of Tregs, which are critical for preventing autoimmunity and maintaining peripheral tolerance (Klatzmann & Abbas, Nat Rev Immunol, 2015). In therapeutic contexts, this complex is targeted by low-dose IL-2 or engineered IL-2 muteins to selectively expand Tregs in patients with autoimmune diseases like systemic lupus erythematosus or graft-versus-host disease (Whang et al., J Immunother Cancer, 2020). Conversely, monoclonal antibodies that block the CD25 subunit are used to prevent acute organ transplant rejection by inhibiting the activation of effector T cells (PMID: 9632444).

Other names

High-affinity interleukin-2 receptorCD25/CD122/CD132 complexIL-2RαβγIL-2 receptor alpha-beta-gamma complex

Selective agonism of the high-affinity IL-2 receptor complex to expand regulatory T cells (Tregs) and restore immune tolerance (PMID: 25848715); or antagonism of the alpha subunit to inhibit T cell activation (PMID: 9632444).