CD122 IL-2R (β chain), IL-2/15Rβ), p75
Molecule TypeAntigen ExpressionMolecular 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
Cell Type Unreduced Reduced
Lymphocytes 70-75 kDa 70 - 75 kDa

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.

Molecule Comment
IL-2 A ligand secreted by activated T cells
IL-15 A ligand whose mRNA is expressed by skeletal muscle, placenta kidney, fibroblasts and activated monocytes
CD25 (IL-2R a) High affinity IL-2R consists of CD25, CD122 and CD132
CD132 (IL-2Rg chain) High affinity IL-2R consists of CD25, CD122 and CD132
Syk Tyrosine kinase are associated with the cytoplasmic region of CD122
Lck Tyrosine kinase are associated with the cytoplasmic region of CD122
Jak1 Tyrosine kinase are associated with the cytoplasmic region of CD122
Stat5 Associated with the cytoplasmic region of CD122

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
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3560P14784
MouseA35052P16297M28052
MouseU22339
RatP26896M55050
Antibodies
MIK-B2   View Reactivity
MIK-B3   View Reactivity

Revised June 25, 2008


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