IFN-y receptor

Table 8.5 Cell types which display an IFN-y receptor on their surface...

The IFN-y receptor (the type II receptor) displays a more limited cellular distribution than that of the type I receptors (Table 8.5). 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. 

An alternative explanation that may also account for the inability of the C-terminal peptide to compete for cell-surface interactions is that its binding site is located not on the extracellular domain of the receptor, but rather on the intracellular domain. The primary differences between the cell-surface form of the IFN-y receptor and (2) the accessibility of the recombinant receptor s cytoplasmic domain. A synthetic peptide corresponding to the membrane proximal region of the cytoplasmic domain of the murine IFN-y receptor was able to bind IFN-y and specifically compete with the binding of IFN-y (95-133) to fixed/permeabilized cells [33]. 

Both the human and the murine IFN-y receptors consist of a ligand-binding subunit and a species-specific cofactor molecule. It is through interaction with this cell-surface receptor complex that IFN-y exerts its biological effects. The IFN-y molecule and its N-terminal peptide IFN-y (1-39) bind specifically to the... 

Szente BE, Subramaniam PS, Johnson HM. Identification of IFN-y receptor binding sites for JAK2 and enhancement of binding by IFN-y and its C-terminal peptide IFN-y(95-133). J Immunol 1995 155 95-133. 

Jarpe MA, Johnson HM. Stable conformation of IFN-y receptor binding peptide in aqueous solution is required for IFN-y antagonist activity. J Interferon Res 1993 13 99. 

Dolhain RJ, ter Haar NT, Hoefakker S, et al. Increased expression of interferon (IFN)-gamma together with IFN-y receptor in the rheumatoid synovial membrane compared with synovium of patients with osteoarthritis. Br J Rheumatol 1996 35 24-32. 

Sakatsume M, Finbloom DS. Modulation of the expression of the IFN-y receptor P-chain controls responsiveness to IFN-y in human peripheral blood T cells. J Immuno 1996 156 4160-6. 

Animal models demonstrate that the IFN-stimulated JAK/STAT signal transduction pathway is critical for controlling CMV infections. STATl knockout mice and IFN-ot receptor/IFN-y receptor double knockout mice, which are deficient in IFN-stimulated signal transduction and biological responses, are exquisitely sensitive to viral infection (Durbin et al. 1996 Presti et al. 1998). In these mice, acute MCMV infection proceeds unchecked and rapidly leads to death. 

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