Interleukin-2 receptor high-affinity complex (IL-2Rαβγ)

The Interleukin-2 (IL-2) receptor high-affinity complex is a heterotrimeric protein assembly consisting of three subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and the common gamma chain (γc, CD132) [1, 5]. This complex is primarily expressed on activated T cells and regulatory T cells (Tregs), where it binds IL-2 with extremely high affinity to initiate critical signaling pathways, including the JAK-STAT, PI3K/Akt, and MAPK pathways [1, 6]. Its biological role is dual: it promotes the rapid expansion and differentiation of effector T cells during an immune response while also maintaining immune tolerance through the development and survival of Tregs [1, 12]. Dysregulation of this receptor system is linked to various pathologies, including autoimmune diseases like multiple sclerosis, organ transplant rejection, and certain hematological malignancies like Adult T-cell leukemia [12, 13, 15]. Therapeutic strategies targeting this complex include monoclonal antibodies like basiliximab that block IL-2 binding to prevent transplant rejection, and recombinant IL-2 (aldesleukin) used to stimulate anti-tumor immunity in cancers like melanoma [9, 12]. However, modulating this target carries risks such as capillary leak syndrome for agonists and increased susceptibility to infections for antagonists [9, 16].

Other names

IL-2RαβγCD25/CD122/CD132 complexTrimeric IL-2 receptorHigh-affinity IL-2 receptorTac/p75/p64 complex

Interleukin-2 receptor agonism; Interleukin-2 receptor alpha subunit antagonism; Targeted cytotoxic fusion protein delivery