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-idiotyp ic antibodies. After a first selection, the monoclonal anti-idiotypic antib ody AA1E5 was chosen to be fully characterized. To the best of our knowledg e 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 comp etes with HuIFN-gamma, but more importantly AA1E5 and its Fv fragment, clon ed and expressed in Escherichia coli, mimic the antiviral activity of HuIFN -gamma. Indeed, 15 mu g of AA1E5 and 2.5 mu g of its Fv fragment had an eff ect comparable to that of 10 IU of HuIFN-gamma in an antiviral assay on A54 9 cells. Sequence comparison between the complementarity determination regi ons of the antibody and the sequence of HuIFN-gamma revealed that both the heavy chain variable domain, V-H , and the kappa light chain variable domai n, V-kappa , have epitopes of 3-4 amino acids that are present in the HuIFN -gamma sequence, some of which contribute to receptor binding, as identifie d by Walter et al. [M. R. Walter, W. T. Windsor, T. L. Nagabhushan, D. J. L undell, C. A. Lunn, P. J. Zauodny & S. K. Narula (1995) Nature 376, 230-235 ].