An anti-idiotypic antibody with an internal image of human interferon-gamma and human interferon-gamma-like antiviral activity.
D9D10, a monoclonal antibody that inhibits the biological activity of human interferon-gamma (IFN-gamma), was used to generate monoclonal anti-idiotypic antibodies. After a first selection, the monoclonal anti-idiotypic antibody AA1E5 was chosen to be fully characterized. To the best of our knowledge this is the first description of a monoclonal antibody with an IFN-gamma-like antiviral activity; AA1E5 competed with IFN-gamma for binding to D9D10 indicating its anti-idiotypic character. However, AA1E5 also fully mimics HuIFN-gamma as it not only binds to the HuIFN-gamma-receptor, where it competes with HuIFN-gamma, but more importantly AA1E5 and its Fv fragment, cloned and expressed in Escherichia coli, mimic the antiviral activity of HuIFN-gamma. Indeed, 15 microg of AA1E5 and 2.5 microg of its Fv fragment had an effect comparable to that of 10 IU of HuIFN-gamma in an antiviral assay on A549 cells. Sequence comparison between the complementarity determination regions of the antibody and the sequence of HuIFN-gamma revealed that both the heavy chain variable domain, VH, and the kappa light chain variable domain, Vkappa, have epitopes of 3-4 amino acids that are present in the HuIFN-gamma sequence, some of which contribute to receptor binding, as identified by Walter et al. [M. R. Walter, W. T. Windsor, T. L. Nagabhushan, D. J. Lundell, C. A. Lunn, P. J. Zauodny & S. K. Narula (1995) Nature 376, 230-235].
Depraetere
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Laboratorium voor Biochemie, KULeuven, Heverlee, Belgium.
Depla
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Haelewyn
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De Ley
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D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000998:Antiviral Agents / Q000276:immunology*; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D000939:Epitopes; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D007371:Interferon-gamma