Antigenic Link Between Human Interferons-α and -β: The Common Epitope 1

Abstract

An until now unobserved consistent antigenic structure, tentatively named "common epitope 1," was detected on molecules of human recombinant (rHu) IFN-α₂ and natural HuIFN-β by testing with monoclonal and polyclonal antibodies. The monoclonal antibody B6, obtained after immunization of BALB/c mice with human fibroblast IFN-β, was capable of binding and neutralizing both IFN-α₂ and natural IFN-β. The neutralizing activity of monoclonal antibody B6 was completely inhibited by a synthetic hexapeptide which corresponded to the amino acid sequence of IFN-α₂ in positions 132–137. Although a corresponding sequence of amino acids in the IFN-β molecule was localized to the region 134–139 and shows only a 66% homology with the assumed IFN-α₂ binding site, lysine at position 132 in IFN-α₂ and at position 134 in IFN-β seems to be crucial for establishment of the common epitope. Its existence was supported by experiments using polyclonal antibodies. Antiserum to IFN-α₂ showed cross-neutralization with IFN-β, and vice versa, antiserum to IFN-β cross-reacted with IFN-α₂. The ability for cross-neutralization by both polyclonal antisera was abolished in the presence of IFN-α₂ hexapeptide SH 132–137. No cross-reacting epitope could be detected on the IFN-α_, molecule. These findings are the first evidence of a homology between human IFNs of α and β types at the antigenic level. They indicate that the antigenic distinction between IFNs of α and β types is not absolute.