Epitope Specificity of Neutralizing Antibodies Against IFN-β

Neutralizing antibodies (NAb), a subset of antibodies against interferon-β (IFN-β) that inhibit activation of the IFN-β receptor, are presumed to bind to the receptor-binding site of IFN-β. The aim of this study was to identify specific epitopes for human NAb and nonneutralizing antibodies (NNAb) on the IFN-β molecule. Thirty-one 12-mer peptides and one 11-mer peptide representing the amino acid sequence of the human IFN-β 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-β1a than in patients treated with IFN-β1b. Our results indicate a qualitative and quantitative difference between NAb an...