Distinct domains of recombinant human IFN-gamma responsible for anti-viral effector function.

A panel of 21 independently isolated neutralizing mAb directed against the human rIFN-gamma (rHuIFN-gamma) was used to characterize those epitopes that are involved in the antiviral function of the rHuIFN-gamma. A sandwich competition assay was developed to determine the cross-reactivities between the mAb. The 125I-labeled mAb were allowed to compete with varying amounts of unlabeled mAb for binding to rHuIFN-gamma under Ag-limiting conditions, and the 50% inhibition endpoints were determined for each of the 21 mAb. The competition of each heterologous mAb relative to the competition of the homologous mAb was determined. By grouping the competition patterns of the 21 mAb, it was apparent that at least two epitopes (E1 and E2) were important to the antiviral function of rHuIFN-gamma. The possibility of the separation of the receptor binding site and signal transduction effector site(s) is discussed.