Therapy-induced antibodies to interferon-alpha 2A recognise its receptor-binding site

Fifty-eight patients with chronic hepatitis B (HB) or C (HC) were treated w ith recombinant human interferon (rIFN)-alpha 2 and their sera were assayed for antibodies to rIFN-alpha 2c. Twelve of these patients produced low tit res and two high titres of the antibodies. We localised the region which wa s recognised by the high-titre therapy-induced antibodies on the IFN molecu le by testing the antibodies with a set of murine monoclonal antibodies (Mo Abs) to IFN-alpha 2 in a competitive radioimmune assay (RIA). Only MoAbs wi th epitopes located in the amino-terminal portion of IFN-alpha 2 could inhi bit the binding of radiolabelled IFN-alpha 2 by patients' sera. Our data in dicate that the therapy-induced antibodies were directed to the receptor-bi nding domain of IFN-alpha 2 formed by amino acids (aa) 30-53. In accordance with this observation, human anti-IFN sera inhibited the binding of rIFN-a lpha 2 to human cells.