IL-2 receptor alpha (IL-2 R 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). IL-2 R alpha is primarily expressed on activated T cells and on regulatory T cells (Treg) (1-3). The rat IL-2 R alpha cDNA encodes a 267 amino acid (aa) precursor that includes a 21 aa signal peptide, a 214 aa extracellular domain (ECD) with two Sushi domains, a 21 aa transmembrane segment, and an 11 aa cytoplasmic domain (4). Within the ECD, rat IL-2 R alpha shares 58% and 81% aa sequence identity with human and mouse IL-2 R alpha, respectively. It shares approximately 15% aa sequence identity with IL-4, -7, -9, -15, and -21 receptor subunits that also complex with gamma _c. IL-2 R beta (CD122) and gamma _c (IL-2 R gamma /CD132) dimerize to form a constitutively expressed intermediate affinity IL-2 receptor (5, 6). By itself, IL-2 R alpha binds IL-2 with low affinity. It associates with IL-2 R beta and  gamma _c to generate a ternary high affinity IL-2 receptor complex (7). A soluble form of IL-2 R 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-2 R alpha are found in some cancers and immune disorders (10). IL-2 R 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-2 R alpha is also required for the development of CD4⁺CD25⁺ Treg which suppress autoreactive CD4⁺ T cells, thereby contributing to peripheral T cell homeostasis (11-13).