Antigenic link between human interferons-alpha and -beta: the common epitope 1.
An until now unobserved consistent antigenic structure, tentatively named "common epitope 1," was detected on molecules of human recombinant (rHu) IFN-alpha 2 and natural HuIFN-beta by testing with monoclonal and polyclonal antibodies. The monoclonal antibody B6, obtained after immunization of BALB/c mice with human fibroblast IFN-beta, was capable of binding and neutralizing both IFN-alpha 2 and natural IFN-beta. The neutralizing activity of monoclonal antibody B6 was completely inhibited by a synthetic hexapeptide which corresponded to the amino acid sequence of IFN-alpha 2 in positions 132-137. Although a corresponding sequence of amino acids in the IFN-beta molecule was localized to the region 134-139 and shows only a 66% homology with the assumed IFN-alpha 2 binding site, lysine at position 132 in IFN-alpha 2 and at position 134 in IFN-beta seems to be crucial for establishment of the common epitope. Its existence was supported by experiments using polyclonal antibodies. Antiserum to IFN-alpha 2 showed cross-neutralization with IFN-beta, and vice versa, antiserum to IFN-beta cross-reacted with IFN-alpha 2. The ability for cross-neutralization by both polyclonal antisera was abolished in the presence of IFN-alpha 2 hexapeptide SH 132-137. No cross-reacting epitope could be detected on the IFN-alpha 1 molecule. These findings are the first evidence of a homology between human IFNs of alpha and beta types at the antigenic level. They indicate that the antigenic distinction between IFNs of alpha and beta types is not absolute.
Kontsek
P
P
Institute of Virology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Borecký
L
L
Kontseková
E
E
Novák
M
M
Krchnák
V
V
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001666:Binding Sites, Antibody / Q000276:immunology; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007370:Interferon Type I; D010446:Peptide Fragments; D011994:Recombinant Proteins