High-affinity interleukin-2 receptor (IL-2Rαβγ) (IL-2Rαβγ)

The high-affinity interleukin-2 receptor (IL-2R) is a heterotrimeric protein complex consisting of three distinct subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and the common gamma chain (γc, CD132) [UniProt P01589, P14784, P31785]. This specific trimeric configuration is characterized by its high affinity for the cytokine IL-2, allowing it to respond to very low concentrations of the ligand, which is a hallmark of regulatory T cells (Tregs) and recently activated effector T cells [Nature Reviews Immunology, 2018]. Upon IL-2 binding, the receptor signals through the JAK1/JAK3 and STAT5 pathways to promote cell survival, proliferation, and the maintenance of immune self-tolerance [Annual Review of Immunology, 2008]. In clinical practice, this receptor is a critical target for modulating the immune system; for instance, low-dose IL-2 therapy is used to selectively expand Tregs in autoimmune diseases like systemic lupus erythematosus and chronic graft-versus-host disease [Immunity, 2013]. Conversely, monoclonal antibodies such as basiliximab target the CD25 subunit to prevent acute organ transplant rejection by blocking the activation of pathogenic T cells. The therapeutic challenge lies in achieving selectivity, as high doses of IL-2 can lead to severe side effects like vascular leak syndrome due to the activation of intermediate-affinity receptors on other cell types.

Other names

Trimeric IL-2 receptorCD25/CD122/CD132 complexIL-2RαβγHigh-affinity IL-2RCD25-CD122-CD132

Agonism of the trimeric receptor complex to expand regulatory T cells for immune tolerance; Antagonism of the IL-2Rα (CD25) subunit to inhibit effector T cell activation in transplantation and autoimmunity; Targeted depletion of CD25-positive cells via toxin-conjugated IL-2 analogs.