II Cytokine Receptor Family

The presence of at least two chains is the common characteristic of many of these receptors. The cytokines having two chain structures exhibit dual affinity although there are some exceptions. The examples of receptors with two chain structures include sharing of y-y subunit of IL-2with IL-4, IL-7, IL-9, IL-15 and IL-21, common (3 chains of IL-3, IL-5 and GM-CSF and common a chain for IL-4 and IL-13. gpl30, which is a second chain required for IL-6-a activity, is also a trigger for several other cytokines. The binding of the cytokine to the double chain renders a dual affinity as is the case for IL-2, IL-3, IL-5, IL-7 and GM-CSF. 

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The class II cytokine receptor family includes receptors for interferon a/P (lEN a/P) and y (lENy) and IL-10. lEN-y immunoreactivity has been found in neurons in the hypothalamus, cerebral cortex, mammilary nuclei, and dorsal tegmentum. Astrocytes and microglia in vitro can be stimulated to express class II histocompatibiHty complex (MHC-II) antigens by lEN-y, which may be involved in the presentation of antigen to T-ceUs by astrocytes. Thus lEN-y may be critical in CNS-immune function and dysfunction especially in regard to neuronal and gHal apoptotic processes. 

Studies have actually revealed two type I interferon receptor polypeptides. Sequence data from cloning studies place both in the class II cytokine receptor family. Both are transmembrane N-linked glycoproteins. Studies using isolated forms of each show that one polypeptide (called the a/p receptor) is capable of binding all type I interferons. The other one (the ap receptor) is specific for IFN-a-B (a specific member of the IFN-a family). Both receptors are present on most cell types. 

IL-22. IL-10-related T cell-derived inducible factor (IL-TIF provisionally designated IL-22) is a cytokine distantly related to IL-10 and is produced by activated T cells (D16). IL-22 receptor, a new member of the interferon receptor family, and CRF2-4, a member of the class II cytokine receptor family, join together to enable IL-22 signaling. Cell lines that respond to IL-22 by activation of STATs 1,3, and 5, but unresponsive to IL-10, have been identified (XI). In contrast to IL-10, IL-22 does not inhibit the LPS-induced production of proinflammatory cytokines by monocytes, but it has a modest inhibitory effect on IL-4 production from Th2 cells (XI). 

IL-IOR is a single-chain receptor. IL-IOR belongs to the class II cytokine receptor family that also includes the IFN receptors (IFNy and IFNap receptors). The extracellular region consists of two homologous fibronectin type III domains that are without the WSXWS motif characteristic of class I cytokine receptors. It is expressed on B cells, thymocytes, and other cellular lines such as mast cells and macrophages. Human IL-IOR mRNA is restricted mostly to hematopoietic cells and cell lines. ... 

The first specifically binds IFNaB (IFNaS, a variety of IFNa) and is known as the IFNaB receptor. The second bmds both IFNa and IFNp and is called the IFNa/j3 receptor. The IFNapR is a member of the class II cytokine receptor family, which also includes the IFNyR, IL-IOR, and tissue factor. The IFNa/ R is also a class II cytokine receptor and contains at least two components that interact with type I IFNs, It is not known if these two receptors are expressed independently on the cell surface or are associated with each other in an IFN receptor complex. The receptors are present on most types of cells. A soluble form of the IFNa/pR has been identified in human serum and urine. 

Fig. 3.1 Families of cytokine receptors the cytokine receptors are classified into five major families immunoglobulin superfamily receptors, type I cytokine receptors, type II cytokine receptors, TNF-like receptors and chemokine receptors. The drawings illustrate their general biochemical structure (see Color Insert)...

NERON D (2003), Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates the class II cytokine receptors and their ligands in mammals and fish , BMC Genomics, 4, 29. 

The interferon receptor superfamily Cytokine receptor type II family Receptors for IFN-cx, -P, -y, IL-10... 

The structural basis by which 7(- functions in binding six distinct cytokines is still not defined, although mutagenesis has localized sites of interaction (Olosz and Malek, 2000, 2002). The only member of this family for which a complex structure exists is IL-4 complex, with its alpha receptor (Hage et al, 1999 Mueller et al, 2002). Molecular modeling of the IL-2, IL-4, and IL-7 complexes with 7 have been constructed based on assumed analogies with the GH paradigm of a site I and site II epitope on... 

The cytokines of the TG F/> family are the activating ligands for the family of TGF/ receptors. This comprises two subfamilies, the type I (T/>R-I) and type II (T/>R-II) receptors. These are transmembrane proteins composed of an extracellular ligand-binding domain, a single transmembrane element, and a cytoplasmic Ser/Thr kinase do-... 

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