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.
Institute of Virology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
P
P
Kontsek
L
L
Borecký
E
E
Kontseková
M
M
Novák
V
V
Krchnák
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