Interleukin-2 receptor subunit alpha (IL-2RA) (IL-2RA)

Interleukin-2 receptor subunit alpha (IL-2RA), also known as CD25, is a 55 kDa transmembrane glycoprotein that serves as the alpha component of the high-affinity interleukin-2 (IL-2) receptor complex (UniProt: P01589). While IL-2RA alone binds IL-2 with low affinity and does not signal, its assembly with the IL-2 receptor beta (CD122) and gamma (CD132) subunits creates a heterotrimeric complex capable of high-affinity binding and robust signal transduction via the JAK/STAT pathway (NCBI Gene: 3559). This receptor is essential for the rapid expansion of activated T-cells and the maintenance of regulatory T-cells (Tregs), making it a central gatekeeper of immune activation and self-tolerance. In clinical pathology, IL-2RA is significantly overexpressed in various hematologic malignancies, including adult T-cell leukemia, Hodgkin lymphoma, and certain non-Hodgkin lymphomas, as well as on activated T-cells during organ transplant rejection and autoimmune flares. Therapeutic strategies targeting IL-2RA include antagonistic monoclonal antibodies like basiliximab, which prevent IL-2-mediated T-cell proliferation to suppress graft rejection, and targeted toxins or antibody-drug conjugates like denileukin diftitox and camidanlumab tesirine designed to selectively eliminate CD25-positive malignant cells. Additionally, the measurement of soluble CD25 in the blood serves as a valuable biomarker for monitoring disease activity and treatment efficacy in inflammatory and neoplastic conditions.

Other names

CD25p55T-cell activation antigenTAC antigenInterleukin-2 receptor alpha chainIDDM10TCGFR

Drugs targeting this molecule primarily act through competitive antagonism, where monoclonal antibodies bind to the alpha subunit to block IL-2 from docking with the high-affinity receptor complex, thereby inhibiting T-cell activation and proliferation (StatPearls: Interleukin 2, 2023). Other modalities include antibody-drug conjugates (ADCs) and immunotoxins that utilize the high expression of CD25 on malignant cells to deliver cytotoxic payloads directly into the cell via receptor-mediated endocytosis (PubMed: 29038343).