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

The high-affinity interleukin-2 receptor (IL-2R) is a heterotrimeric protein complex consisting of the alpha (CD25), beta (CD122), and gamma (CD132) subunits (UniProt P01589, P14784, P31785). It is primarily characterized by its constitutive expression on regulatory T cells (Tregs), which allows these cells to respond to very low concentrations of the cytokine interleukin-2 (IL-2) (Klatzmann & Abbas, 2015, Nature Reviews Immunology). In contrast, effector T cells and natural killer cells typically express the intermediate-affinity dimeric receptor (CD122 and CD132) and only upregulate CD25 upon activation (Abbas et al., 2018, Science Immunology). This biochemical distinction is exploited therapeutically to selectively expand the Treg population, thereby restoring immune tolerance in autoimmune and inflammatory diseases. Drugs targeting this pathway include low-dose recombinant IL-2 and engineered IL-2 muteins designed to favor binding to the high-affinity trimeric complex over the dimeric form (He et al., 2021, Frontiers in Immunology). Successful modulation of this receptor complex holds potential for treating conditions like systemic lupus erythematosus, graft-versus-host disease, and type 1 diabetes by suppressing pathogenic immune responses without inducing global immunosuppression (Tahvildari & Dana, 2019, Frontiers in Pharmacology).

Other names

CD25/CD122/CD132 complexIL-2R alpha/beta/gammaHigh-affinity IL-2RIL-2 receptor

Selective expansion of regulatory T cells (Tregs) via activation of the JAK-STAT5 signaling pathway upon binding to the high-affinity IL-2Rαβγ complex (Abbas et al., 2018, Science Immunology).