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

The high-affinity interleukin-2 receptor (IL-2R) is a heterotrimeric protein complex composed of three distinct subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and the common gamma chain (γc, CD132) (StatPearls: Interleukin-2). While the dimeric IL-2Rβγ complex possesses intermediate affinity for IL-2, the inclusion of the α-chain (CD25) increases the binding affinity by roughly 100-fold, making the complex highly sensitive to low concentrations of IL-2 (PubMed: 22391954). This high-affinity form is transiently expressed on the surface of activated T cells and constitutively on regulatory T cells (Tregs), where it plays a pivotal role in lymphocyte homeostasis and the immune response (UniProt: P01589). Upon IL-2 binding, the receptor triggers intracellular signaling primarily through the JAK1/JAK3 and STAT5 pathways, leading to cellular proliferation and survival (PubMed: 17110311). Therapeutically, the receptor is targeted by monoclonal antibodies to prevent organ transplant rejection and by IL-2 agonists to enhance anti-tumor immunity in cancers like melanoma and renal cell carcinoma (NIH: LiverTox; PubMed: 28434937).

Other names

CD25/CD122/CD132 complexTrimeric IL-2 receptorIL-2RαβγInterleukin-2 receptor alpha/beta/gamma heterotrimerHigh-affinity IL-2R

Antagonists like basiliximab and daclizumab bind to the CD25 subunit of the high-affinity receptor complex to competitively inhibit interleukin-2 (IL-2) binding, thereby suppressing T-cell activation and proliferation (PubMed: 10073387). Agonists such as aldesleukin (recombinant IL-2) bind to the trimeric receptor complex to activate the JAK-STAT signaling pathway, promoting the expansion of effector T cells for cancer immunotherapy or regulatory T cells in autoimmune contexts (PubMed: 30617336).