Interleukin-2 receptor, high-affinity form (IL-2Rαβγ)

The high-affinity Interleukin-2 receptor (IL-2R) is a heterotrimeric protein complex essential for the regulation of the adaptive immune system (Malek, 2008 [6]). It consists of three distinct subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and the common gamma chain (γc, CD132) (UniProt: P01589, P14784, P31785 [1, 2, 3]). While the β and γ subunits form an intermediate-affinity receptor, the addition of the α subunit creates the high-affinity form, which is primarily expressed on activated T cells and regulatory T cells (Tregs) (Liao et al., 2013 [7]). Binding of IL-2 to this complex triggers intracellular signaling through the JAK/STAT, PI3K/AKT, and MAPK pathways, driving T-cell proliferation, survival, and functional differentiation (StatPearls, 2023 [4]). In clinical practice, this receptor is a major target for immunosuppression in organ transplantation, using monoclonal antibodies like basiliximab to block the CD25 subunit (FDA: Simulect [8]). Conversely, IL-2 agonists such as aldesleukin are used in oncology to stimulate anti-tumor T-cell responses, though their use is often limited by toxicities such as capillary leak syndrome (NCBI: Aldesleukin [9]).

Other names

CD25/CD122/CD132 complexIL-2R alpha/beta/gammaHigh-affinity IL-2 receptorT-cell growth factor receptor

Drugs targeting the high-affinity IL-2 receptor act by either blocking the binding of IL-2 to the CD25 subunit to prevent T-cell activation (antagonists) or by mimicking IL-2 to stimulate the JAK/STAT signaling pathway for immune activation (agonists) (StatPearls, 2023 [4]). Some therapies also utilize the receptor for targeted delivery of cytotoxic payloads to CD25-expressing malignant cells (NCBI: Denileukin diftitox [10]).