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Eur Cytokine Netw. 2000 Dec;11(4):560-73.

Localization of a receptor nonapeptide with a possible role in the binding of the type I interferons.

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  • 1Laboratory of Viral Oncology, CNRS-UPR 9045, Institut de Recherches sur le Cancer/IFR Y1221, 94801 Villejuif, France. eid@infobiogen.fr

Abstract

Interferons (IFNs) in common with other cytokines activate Janus tyrosine kinases and latent STAT transcription factors upon binding to their cell surface receptor. Type I IFNs bind to a receptor composed of two transmembrane polypeptides, IFNAR1 and IFNAR2, which belong to the class II cytokine receptor family that also includes the cellular receptors for IFN-gamma, interleukin-10 and coagulation protease factor VII (tissue factor). The extracellular domain of the type I IFN receptor chain IFNAR1, has four fibronectin type-III sub-domains. Human IFNAR1 has intrinsic weak affinity for type I IFNs and plays an essential role in transmembrane signaling, formation of a high affinity complex with IFN and the modulation of ligand specificity. In order to characterise the ligand binding site on IFNAR1 we analysed the epitope recognized by the anti-IFNAR1 mAb, 64G12, which inhibits the binding and biological activities of both IFN-alpha and IFN-beta. The target peptide recognized by the 64G12 mAb was determined by screening a set of 48 overlapping peptides covering the first two subdomains (residues 23-229) of the extracellular region of IFNAR1. The results of this study show that the peptide (FSSLKLNVY), localized within the first sub-domain (residues 89-97) of IFNAR1, which is recognized by the 64G12 mAb, most likely overlaps a site to which both IFN-alpha and IFN-beta bind in the ligand-receptor complex. Thus, since the 64G12 mAb can neutralize the biological activities of all the type I IFNs tested, we suggest that the target peptide recognized by the 64G12 mAb, is a possible anchorage point on IFNAR1, common to binding of both IFN-alpha and IFN-beta.

PMID:
11125298
[PubMed - indexed for MEDLINE]
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