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Interleukin-2 receptor subunit alpha (IL2RA), also known as CD25, is a type I transmembrane protein that serves as the high-affinity component of the trimeric interleukin-2 (IL-2) receptor complex (UniProt: P01589). It is constitutively expressed at high levels on regulatory T cells (Tregs) and is transiently upregulated on effector T cells following antigen-induced activation (NCBI Gene: 3559). IL2RA is essential for the maintenance and competitive fitness of Tregs, which are critical for maintaining peripheral immune tolerance and preventing autoimmunity (PubMed: 29038280). In clinical medicine, IL2RA is a major therapeutic target; monoclonal antibodies such as basiliximab are used to prevent acute organ transplant rejection by blocking the IL-2 signal required for effector T cell proliferation (StatPearls: Basiliximab). Conversely, low-dose IL-2 and IL-2 muteins are employed to selectively expand the IL2RA-high Treg population to treat autoimmune conditions like systemic lupus erythematosus (PubMed: 31534203). Furthermore, IL2RA-targeted antibody-drug conjugates, such as camidanlumab tesirine, are being investigated for their ability to deplete immunosuppressive Tregs within the tumor microenvironment to enhance anti-tumor immune responses (PubMed: 33067318).
Competitive antagonism of IL-2 binding to the high-affinity receptor; Selective agonism of the IL-2 receptor to expand regulatory T cell populations; Targeted cytotoxic depletion of CD25-expressing cells via antibody-drug conjugates.
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