title: Epitope specificity of neutralizing antibodies against IFN-beta.
abstract: Neutralizing antibodies (NAb), a subset of antibodies against interferon-beta (IFN-beta) that inhibit activation of the IFN-beta receptor, are presumed to bind to the receptor-binding site of IFN-beta. The aim of this study was to identify specific epitopes for human NAb and nonneutralizing antibodies (NNAb) on the IFN-beta molecule. Thirty-one 12-mer peptides and one 11-mer peptide representing the amino acid sequence of the human IFN-beta molecule were used as antigens in an ELISA antibody assay. Significant antibody binding was observed at residues 1-12, 121-132, and 151-162. NNAb and NAb recognized residues 121-132 with equal frequency, but NAb had higher titers. NAb bound significantly more frequently to residues 1-12 and 151-162. There was a significant positive correlation between NAb titers and titers against residues 1-12. Binding to residues 1-12 was more pronounced in patients treated with IFN-beta1a than in patients treated with IFN-beta1b. Our results indicate a qualitative and quantitative difference between NAb and NNAb, with special emphasis on the recognition of different epitopes.
authors.affiliation: Department of Neurology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gneiss
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.forename: Andreas
authors.initials: A
authors.lastname: Lutterotti
authors.forename: Rainer
authors.initials: R
authors.lastname: Ehling
authors.forename: Robert
authors.initials: R
authors.lastname: Egg
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D000918:Antibody Specificity / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology* / Q000627:therapeutic use; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D000939:Epitopes; D007155:Immunologic Factors; D011994:Recombinant Proteins; D016899:Interferon-beta