Distinct effect of pH 2 on a common antigenic structure found in human interferons-alpha 1 and -alpha 2 in the region 30-35.
The antigenic similarity between molecules of recombinant human interferon-alpha 1 (IFN-alpha 1) and recombinant human IFN-alpha 2 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-alpha molecule around residues 30-35. Following pH 2 treatment, the biological activity of both IFN-alpha 1 and IFN-alpha 2 was retained but the antigenic relatedness between corresponding sequences 30-35 was diminished. The common structure on the IFN-alpha 1 molecule proved acid stable and the mAb 1-46 retained the ability to neutralize the pH 2 treated IFN-alpha 1. However, the neutralization of pH 2-treated IFN-alpha 2 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-alpha 2 molecule. We conclude that pH 2 may induce a conformational rearrangement of the IFN-alpha 2 molecule, resulting in an altered tertiary structure with deviating antigenic characteristics.
Kontsek
P
P
Institute of Virology, Slovak Academy of Sciences, Bratislava.
Borecký
L
L
Novák
M
M
Kontseková
E
E
Máciková
I
I
Krchnák
V
V
D000143:Acids; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive / Q000276:immunology; D002455:Cell Division; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007370:Interferon Type I / Q000737:chemistry* / Q000276:immunology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011487:Protein Conformation; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D000143:Acids; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins