Interactions between hepatitis B virus and polymeric human albumin. I. Production of monoclonal anti-idiotypes (anti-anti-polymeric human albumin) which recognize hepatitis B virus surface antigen.

In an attempt to characterize the polymeric human albumin (polyHSA) receptor expressed on hepatitis B virus and hepatocytes, we have used a human anti-polyHSA IgG to generate monoclonal anti-idiotypes (anti-Id) which bear the internal image of polyHSA and mimic its binding activity. Two monoclonal anti-Id antibodies, 63.14 and 70.F9, were strongly reactive in both radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) with the F(ab')2 of the immunogen as well as with purified hepatitis B surface antigen (HBsAg) expressing various subtypes. The specificity of the binding of anti-Id to HBsAg was confirmed in direct ELISA and by Western blot analysis. These experiments also showed that the anti-Id bind to a site expressed on the major 24-kDa protein of HBsAg particles, and that this recognition is specifically inhibited by polyHSA. Experiments on cellular staining and radioimmunoprecipitation on HBsAg-positive and -negative cell lines showed that the anti-Id recognize intracellular HBsAg but not other liver cell proteins, including the putative polyHSA receptor. These data indicate, therefore, that the monoclonal anti-Id mimic the binding activity of polyHSA and recognize its binding site on the virus. The inability of both anti-Id to react with the hepatocyte surface suggests either the absence of a specific hepatic polyHSA receptor or the expression of one with a different configuration.