IFN receptors

Although there has been substantial success using IFN for the treatment of some cancels, until this point, the great majority of tumors are resistant or show an initial moderate response soon followed by disease progression under treatment. One likely reason for resistance is the progredient loss of susceptibility to IFN, which may be caused by downregulation of IFN receptors or perturbation of intracellular DFN-signaling pathways, a phenomenon also known from in vitro studies. 

Studies have actually revealed two type I IFN 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/jS-receptor) is capable of binding all type I IFNs. The other one (the a S-receptor) is specific for IFN-aB (a specific member of the IFN-a family). Both receptors are present on most cell types. 

Interferon, in particular type I IFN, is well adapted to its anti-viral function. Upon entry into the body, viral particles are likely to quickly encounter IFN-a/jS-producing cells, including macrophages and monocytes. This prompts IFN synthesis and release. These cells act like sentries, warning other cells of the viral attack. Most body cells express the type I IFN receptor, thus the released IFN-a or will induce an anti-viral state in such cells. 

Next, it was determined whether the same active regions of IFN- were involved in additional systems. The Type I IFN receptor on cells has been reported to be somewhat more promiscuous than on other cell types [16] therefore, vesicular stomatitis challenge of Fc-9 cells was performed. Only the carboxy-terminal peptide inhibited IFN- activity in this system [17]. This suggested that it was the carboxy-terminus that was crucial to receptor interaction. In studies examining IFN-T-treated feline immunodeficiency virus infected FeT-1 cells and human immunodeficiency virus-infected peripheral... 

Inhibition of cell-adhesion Inhibition of IFN-receptor binding... 

Marchetti M, Monier MN, Fradagrada A, Mitchell K, Bayche- 126. tier F, Bid P, Johannes L, Lamaze C. Stat-mediated signaling induced by type I and type II interferons (IFNs) is differentially controlled through lipid microdomain association and clathrin-dependent endocytosis of IFN receptors. Mol. Biol. Cell 2006 17 2896-2909. 

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. 

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