The interferon receptors

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. 

The IFN-y receptor (the type II receptor) displays a more limited cellular distribution than that of the type I receptors (Table 4.5). This receptor is a transmembrane glycoprotein of molecular mass 50 kDa, which appears to function as a homodimer. The extracellular IFN-y-binding region consists of approximately 200 amino acid residues folded into two homologous domains. Initiation of signal transduction also requires the presence of a second transmembrane glycoprotein, known as AF-1 (accessory factor 1), which associates with the extracellular region of the receptor. 

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

Roisman LC, Piehler J, Trosset JY et al (2001) Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking. Proc Natl Acad Sci U S A 98 13231-13236... 

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). 

Some cytokine receptors can directly initiate signal transduction upon binding of ligand. In other cases additional elements are involved. For many receptors, the exact intracellular events triggered upon ligand binding remain to be elucidated. However, the molecular details of signal transduction pathways for others (e.g. the interferons) are now understood... 

No one interferon will display all of these biological activities. Effects are initiated by the binding of the interferon to its specific cell surface receptor present in the plasma membrane of sensitive cells. IFN-a and -P display significant amino acid sequence homology (30 per cent), bind to the same receptor, induce similar biological activities and are acid stable. For these reasons, IFN-a and IFN-P are sometimes collectively referred to as type I interferons, or acid-stable interferons. 

Not all type I interferons induce exactly the same range of responses, and the antiviral to antiproliferative activity ratio differs from one type I interferon to another. As all bind the same receptor, the molecular basis by which variation in biological activities is achieved is poorly understood as yet. 

Li, J. and Roberts, M. 1994. Interferon-T and interferon-a interact with the same receptors in bovine endometrium. Journal of Biological Chemistry 269(18), 13 544-13 550. 

Based upon recent controlled studies, there is considerable evidence that opioids such as morphine induce substantial effects on immune status. For example, it has been shown that morphine administration is associated with alterations in a number of immune parameters, such as natural-killer cell activity [12,13], proliferation of lymphocytes, [13, 14] antibody production [15,16], and the production of interferon [17]. Studies in our laboratory have shown that acute morphine treatment in rats suppresses splenic lymphocyte proliferative responses to both T- and B-cell mitogens, splenic natural-killer cell activity, blood lymphocyte mitogenic responsiveness to T-cell mitogens, and the in vitro production of the cytokines interleukin-2 and interferon-y [18-22], Furthermore, the immune alterations induced by morphine are dose-dependent and antagonized by the opioid-receptor antagonist, naltrexone (e.g., [22]). 

T Yu, Y Xiao, Y Bai, Q Ru, G Luo, MP Dierich, YH Chen. Human interferon-beta inhibits binding of HIV-1 gp41 to lymphocyte and monocyte cells and binds the potential receptor protein P50 for HIV-1 gp41. Immunol Lett 73 19-22, 2000. 

Many cytokines exhibit redundancy, i.e. two or more cytokines can induce a similar biological effect. Examples include TNF-a and -P, both of which bind to the same receptor and induce very similar if not identical biological responses. This is also true of the interferon-a family of proteins and interferon-/ , all of which bind the same receptor. 

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