CD25 consists of three domains: extracellular (N-terminus), transmembrane (alpha-helix) and cytoplasmic (C-terminus). However, while extracellular part is able to function as a binding site for Interleukin-2, short cytoplasmic domain lacks an ability to induce intracellular signalling and therefore needs to oligomerise with other IL-2 receptor subunits. The interleukin-2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL-2 receptor complex (Kd ~10−11M). Homodimeric alpha chains (IL2RA) result in low-affinity receptor (Kd ~10−8M) with no signalling ability, while dimeric beta (IL2RB) and gamma chains (IL2RG) produce a medium-affinity receptor (Kd ~10−9M). Moreover, CD25 is an exclusive subunit that entirely binds IL-2, while CD132 binds the shared γc family cytokines (IL-4, IL-7, IL-9, IL-15 and IL-21), and the CD122 subunit binds also IL-15. Soluble IL2RA has been isolated and determined to result from extracellular proteolysis during activation of T lymphocytes. Also, alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is currently unknown. Signalling cascade of Interleukin-2 Receptor Interleukin-2 can interact with intermediate-affinity dimeric IL-2 receptor, which consists of beta (CD122) and gamma (CD132) chains or with high-affinity trimeric complex, where also alpha subunit (CD25) constructs the IL-2 receptor and provides enhanced specific binding force. After activation of the receptor by its ligand, heterodimerisation of beta and gamma intracellular domains takes place. This coupling of subunits brings together Janus kinases JAK1 and JAK3, considering their association with respective cytoplasmic parts of beta and gamma subunits. Downstream phosphorylation leads to initiation of three signalling pathways: JAK-STAT pathway, PI3K/Akt/mTOR pathway and Ras/Raf/MEK/ERK (MAPK) pathway. Regarding JAK-STAT pathway, particular signal transducers and activators of transcription participate in this signalling cascade: STAT5, STAT1 and STAT3 and after dimerisation, they translocate to nucleus to perform transcription factor functions. All three signalling pathways are important for diverse cellular regulations, in terms of increased survival (anti-apoptotic effect), proliferation and cell growth, transcriptional regulation and cell differentiation. T lymphocytes are influenced by IL-2R signalling in case of CD4+ T helper subtype differentiation: promoting Th1, Th2, Th9, Tfr (T follicular regulatory cells) and suppressing Th17, Tfh ( T follicular helper cells). Additionally, strength of IL-2R signalling in CD8+ T cytotoxic lymphocytes may be connected to phenotypic fate of these cells for effector and memory T cells formation. Clinical significance Roifman's group was the first to identify immunological consequences of CD25 loss and the patient has suffered from chronic infections and