Epitope specificity of neutralizing antibodies against IFN-beta.
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.
Gneiss
Claudia
C
Department of Neurology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Reindl
Markus
M
Berger
Thomas
T
Lutterotti
Andreas
A
Ehling
Rainer
R
Egg
Robert
R
Deisenhammer
Florian
F
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
D000906:Antibodies; D000939:Epitopes; D007155:Immunologic Factors; D011994:Recombinant Proteins; D016899:Interferon-beta