Description
IL-2 receptor alpha (IL2R alpha), also known as CD25, is a 55 kDa type I membrane glycoprotein that belongs to the family of cytokine receptors that utilize the common gamma chain subunit (gamma c). Human IL-2R alpha cDNA encodes a 213 amino acid (aa) precursor with a 21 aa signal peptide and a 192 aa extracellular region. The ECD of Human IL-2R alpha shares a 59% amino acid sequence identity with the ECD of mouse and rat IL2R alpha, respectively. IL‑2R alpha is primarily expressed on activated T cells and on regulatory T cells (Treg) (1-3). IL-2R beta (CD122) and gamma c (IL-2R gamma /CD132) dimerize to form a constitutively expressed intermediate affinity IL-2 receptor (4, 5). By itself, IL-2R alpha binds IL-2 with low affinity. IL-2R alpha makes no contacts with IL-2R beta or gamma c, and only minor changes are observed in the IL-2 structure in response to receptor binding. These findings support the principal role of IL-2R alpha to deliver IL-2 to the signaling complex and act as regulator of signal transduction (6, 7). A soluble form of IL‑2R alpha can be generated by proteolytic cleavage of the cell surface receptor, rendering the T cell unresponsive to IL-2 (8, 9). Increased serum levels of soluble IL‑2R alpha are found in some cancers and immune disorders (10). IL-2R alpha is required for activation induced cell death (AICD) of naive T cells, a mechanism responsible for deleting autoreactive T cell clones (11, 12). IL-2R alpha is also required for the development of CD4+CD25+ Treg which suppresses autoreactive CD4+ T cells, thereby contributing to peripheral T cell homeostasis (11-13)