An antiâidiotypic antibody with an internal image of human interferonâγ and human interferonâγâlike antiviral activity
2000
Depraetere, Hilde | Depla, Erik | Haelewyn, Joost | Ley, Marc de
D9D10, a monoclonal antibody that inhibits the biological activity of human interferonâγ (IFNâγ), was used to generate monoclonal antiâidiotypic antibodies. After a first selection, the monoclonal antiâidiotypic 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 IFNâγâlike antiviral activity; AA1E5 competed with IFNâγ for binding to D9D10 indicating its antiâidiotypic character. However, AA1E5 also fully mimics HuIFNâγ as it not only binds to the HuIFNâγâreceptor, where it competes with HuIFNâγ, but more importantly AA1E5 and its Fv fragment, cloned and expressed in Escherichia coli, mimic the antiviral activity of HuIFNâγ. Indeed, 15âµg of AA1E5 and 2.5âµg of its Fv fragment had an effect comparable to that of 10 IU of HuIFNâγ in an antiviral assay on A549 cells. Sequence comparison between the complementarity determination regions of the antibody and the sequence of HuIFNâγ revealed that both the heavy chain variable domain, VHâ, and the kappa light chain variable domain, Vκâ, have epitopes of 3–4 amino acids that are present in the HuIFNâγ 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) Nature376, 230–235].
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