An anti-idiotypic antibody with an internal image of human interferon-γ and human interferon-γ-like antiviral activity

Abstract

D9D10, a monoclonal antibody that inhibits the biological activity of human interferon-γ (IFN-γ), 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-γ-like antiviral activity; AA1E5 competed with IFN-γ for binding to D9D10 indicating its anti-idiotypic character. However, AA1E5 also fully mimics HuIFN-γ as it not only binds to the HuIFN-γ-receptor, where it competes with HuIFN-γ, but more importantly AA1E5 and its Fv fragment, cloned and expressed in Escherichia coli, mimic the antiviral activity of HuIFN-γ. Indeed, 15 μg of AA1E5 and 2.5 μg of its Fv fragment had an effect comparable to that of 10 IU of HuIFN-γ in an antiviral assay on A549 cells. Sequence comparison between the complementarity determination regions of the antibody and the sequence of HuIFN-γ revealed that both the heavy chain variable domain, V(H), and the kappa light chain variable domain, V(K), have epitopes of 3-4 amino acids that are present in the HuIFN-γ 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. Am. Lunn, P. J. Zauodny and S. K. Namla (1995) Nature 376, 230-235].