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

作者：Depraetere H; Depla E; Haelewyn J; De Ley M^*

来源：European Journal of Biochemistry, 2000, 267(8): 2260-2267.

DOI：10.1046/j.1432-1327.2000.01231.x

• anti-idiotypic antibody
• interferon-gamma
• antiviral activity
• internal image

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 mu g of AA1E5 and 2.5 mu g 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, V-H , and the kappa light chain variable domain, 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 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].

• 出版日期2000-4