| CD122 | IL-2R (β chain), IL-2/15Rβ), p75 |
| Molecule Type | Antigen Expression | Molecular Weight Min / Max |
| Non-lineage Restricted Molecule Type 1 glycoprotein | NK Cell B Cell Monocyte Macrophage Lymphocyte T Cell | 70 / 70 75 / 75 |
Expression | ||||||||||||||||||||||||||||||
| CD122 is expressed in association with IL-2R and IL-15R a chains. It is expressed on activated cells including T and B cells, macrophages and monocytes. CD122 is expressed at low levels on lymphocytes and NK cells and a subpopulation of resting T cells but is upregulated by a 5- to 10-fold following T cell activation. | ||||||||||||||||||||||||||||||
Structure | ||||||||||||||||||||||||||||||
| MOLECULAR FAMILY NAME: Belongs to the hemopoietin superfamily. CD122 is a single-pass type-1 β chain 525 aa glycopeptide. It contains a 214 aa extracellular region which contains 4 conserved cysteine residues, a fibronectin type-3 containing a WSXWS (trp-ser-X-trp-ser) motif, a 25 aa transmembrane domain and a 286 cytoplasmic domain which has at least 3 unique regions like serine-rich, acidic and proline-rich regions with 6 cytoplasmic tyrosine residues which are present in the acidic and proline-rich regions. One of the 3 subunits, which in various combinations give rise to receptors capable of binding IL-2 and/or IL15 with varying affinity. The functional IL-15R and IL-2 are heterotrimeric complexes comprised of the IL-15Ra chain, CD122 IL-2Rb chain and CD132 g chain. The IL-15Ra chain contains 1 extracellular CCP domain, followed by a region rich in Ser and Thr residues, and has a 41 aa cytoplasmic tail that is dispensable for signal transduction. CD122 is involved in T cell-mediated immune responses and is present in 3 forms with an ability to bind IL-2. The low affinity form is a monomer of the α subunit and is not involved in signal transduction. The intermediate affinity form consists of an α/β subunit heterotrimer, while the high affinity form consists of an α/β/γ heterotrimer. Both the intermediate and high affinity forms of the receptor are unvolved in receptor-mediated endocytosis and transduction of mitogenic signals from IL-2. CD122 is a cytokine receptor belonging to the hempopoietin receptor superfamily and the Ig gene superfamily. MOLECULAR MASS
POST-TRANSCRIPTIONAL MODIFICATION Alternatively spliced yields 3 different isoforms of the human IL-15Ra chain that have been cloned. POST-TRANSLATIONAL MODIFICATION CD122 is phosphorylated upon ligand binding. | ||||||||||||||||||||||||||||||
Ligands | ||||||||||||||||||||||||||||||
| LIGANDS AND MOLECULES ASSOCITED WITH CD122 The functional high affinity of IL-2R kDa = 10 pM is composed of a non-covalently associated CD25/CD122/CD132 heterotrimer. The CD122/CD132 heterodimer binds IL-2R with an intermediate affinity of kDa = 1 nM. Intermediate affinity receptors are important for IL-2R signaling. The IL-15Ra chain binds IL-15R with a high affinity of kDa = 10 pM. However, the interaction between the IL-15Ra chain and CD122/C132 is required to form a functional high affinity IL-15R capable of mediating signal transduction. High concentrations of IL-15R, 450 ng/ml, can bind to and signal through a complex of CD122/CD132 in the absence of the IL-15Ra chain.
Jak3 tyrosine kinase is also involved in signaling via its association with the cytoplasmic region of CD132. | ||||||||||||||||||||||||||||||
Function | ||||||||||||||||||||||||||||||
| The biological effect of CD122 ligation will depend on whether IL-2 or IL-15 is bound and is critical for signaling. Oligomerization of CD122 subunits activates several tyrosine kinases. The serine-rich region has binding sites for Janus family kinases that induce mitogenic and survival signals. The WSXWS motif of CD122 is essential for IL-2R binding, while its cytoplasmic Ser-rich region is necessary for signal transduction. CD122 associates with the Lck tyrosine kinase through its cytoplasmic acidic region. The interaction of IL-2 with its high affinity receptor induces Tyr phosphorylation of CD122 and several other proteins. The acidic-region of the cytoplasmic domain has binding sites required for induction of NK cell cytotoxicity and downregulation of T cell proliferation. CD122 induces the activation and proliferation of T and B cells, thymocytes, NK cells, and macrophages and plays a role in T cell mediated immune reponse. The proline-rich region is involved in the activation Stat3 and Stat5. When phosphorylated, these factors dimerize and localize to the nucleus and induce the transcription of genes involved in NK-cell and intraepithelial lymphocyte development as well as upregulation of IL-2 expression. IL-15R shares biological activities with IL-2R, such as the activation and proliferation of T cells, generation of cytotoxic T cells and lymphokine-activated killer (LAK) cells, and the proliferation of NK and B cells. BIOCHEMICAL ACTIVITY: CD122 is one of the critical subunits of IL-2R and IL-15R. DISEASE RELEVANCE AND FUNCTION OF CD122 IN INTACT ANIMAL CD122 deficient mice display a dramatic reduction in NK and intraepithelial lymphocytes cells due to impaired differentiation. These mice develop severe autoimmune disorders and infiltrative granulocytopoiesis and virtual absence of NK cells. Combined anti-CD122 and anti-CD25 therapy has been used in the treatment of autoimmune disorders and allograft rejection. Four cell lines of human T cell lymphoma/leukemia origin 2 IL-2R subunits are compartmented together with HLA glycoproteins and CD48 molecules in the plasma membrane. Anti-CD122 monoclonal antibodies have been used in clinical trials for large granular lymphocytic leukemia. | ||||||||||||||||||||||||||||||
Comments | ||||||||||||||||||||||||||||||
| The IL-15R a chain and CD25 genes have a similar intron/exon organization and are closely linked in both the human and mouse. IL-15R a chain mRNA is expressed on a wide range of cell types, in contrast to CD25. Since CD122 and CD132 are essential for IL-15R signaling in hematopoietic cell types and their expression patterns are more restricted than the IL-15Ra chain, the possibility exists that the IL-15Ra may associate with alternative signaling subunits in other cell types. MOLECULAR INTERACTIONS - PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD122: No information. SUBSTRATES: No information. ENZYMES WHICH MODIFY CD122: No information. | ||||||||||||||||||||||||||||||
Database accession numbers | ||||||||||||||||||||||||||||||
Revised June 25, 2008
|
||||||||||||||||||||||||||||||