title: Localization of a receptor nonapeptide with a possible role in the binding of the type I interferons.
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.
authors: Laboratory of Viral Oncology, CNRS-UPR 9045, Institut de Recherches sur le Cancer/IFR Y1221, 94801 Villejuif, France. eid@infobiogen.fr
authors: P
authors: P
authors: Eid
authors: J A
authors: JA
authors: Langer
authors: G
authors: G
authors: Bailly
authors: R
authors: R
authors: Lejealle
authors: J
authors: J
authors: Guymarho
authors: M G
authors: MG
authors: Tovey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016466:CHO Cells; D019556:COS Cells; D002417:Cattle; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D018604:Epitope Mapping; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology; D053613:Janus Kinase 1; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D007140:Immunoglobulin Fab Fragments; D007370:Interferon Type I; D016898:Interferon-alpha; D008565:Membrane Proteins; D009842:Oligopeptides; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1