Distinct Effect of pH 2 on a Common Antigenic Structure Found in Human Interferons-α 1 and -α 2 in the Region 30–35

Abstract

The antigenic similarity between molecules of recombinant human interferon-α₁ (IFN-α₁) and recombinant human IFN-α₂ was demonstrated with neutralizing monoclonal antibody (mAb) 1-46. The common epitope for the mAb 1-46 was localized into amino-terminal region of IFN-α molecule around residues 30–35. Following pH 2 treatment, the biological activity of both IFN-α₁ and IFN-α₂ was retained but the antigenic relatedness between corresponding sequences 30–35 was diminished. The common structure on the IFN-α₁ molecule proved acid stable and the mAb 1–46 retained the ability to neutralize the pH 2 treated IFN-α₁. However, the neutralization of pH 2-treated IFN-α₂ by specific antibody was completely suppressed. These results complemented our earlier finding of the dramatic effect of acidic pH on the antigenic structure of region 132–137 of the IFN-α₂ molecule. We conclude that pH 2 may induce a conformational rearrangement of the IFN-α₂ molecule, resulting in an altered tertiary structure with deviating antigenic characteristics.