Interleukin-2 receptor (IL-2R) high-affinity trimer (IL-2Rαβγ)

The high-affinity Interleukin-2 receptor (IL-2R) is a heterotrimeric protein complex composed of three subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and IL-2Rγ (CD132) [1]. It is primarily expressed on activated T cells and natural killer (NK) cells, where it plays a critical role in mediating the effects of Interleukin-2 (IL-2), a key cytokine for lymphocyte proliferation and differentiation [2]. Upon IL-2 binding, the receptor triggers the JAK/STAT, PI3K/Akt, and MAPK/ERK signaling pathways, which are essential for the expansion of effector T cells and the maintenance of regulatory T cells (Tregs) [3]. In clinical practice, this receptor is a major therapeutic target; monoclonal antibodies like basiliximab block the CD25 subunit to prevent organ transplant rejection by inhibiting T-cell activation [4]. Conversely, IL-2 agonists are used in oncology to boost the immune system's ability to fight cancer, although their use is often limited by toxicities such as capillary leak syndrome [5]. The balance of signaling through this receptor is vital for maintaining immune homeostasis and preventing both autoimmunity and malignancy [6]. Sources: [1] UniProt (P01589, P14784, P31785); [2] Liao, W., et al. (2013) Immunity; [3] Malek, T. R. (2008) Annual Review of Immunology; [4] Waldmann, T. A. (2006) Nature Reviews Immunology; [5] Krieg, C., et al. (2010) Current Opinion in Immunology; [6] Spolski, R., et al. (2018) Nature Reviews Immunology.

Other names

CD25/CD122/CD132 complexHigh-affinity IL-2 receptorIL-2R alpha/beta/gammaIL2R trimerActivated T-cell receptor complex

Drugs targeting the high-affinity IL-2 receptor function as either antagonists to block IL-2 binding and inhibit T-cell mediated immune responses, or as agonists to mimic IL-2 signaling and promote the expansion of effector immune cells for oncology applications.