SPONTANEOUS DEVELOPMENT OF ANTI-HEPATITIS-B VIRUS ENVELOPE (ANTIIDIOTYPIC) ANTIBODIES IN ANIMALS IMMUNIZED WITH HUMAN LIVER ENDONEXIN-II OR WITH THE F(AB')(2) FRAGMENT OF ANTI-HUMAN LIVER ENDONEXIN-II IMMUNOGLOBULIN-G - EVIDENCE FOR A RECEPTOR-LIGAND-LIKE RELATIONSHIP BETWEEN SMALL HEPATITIS-B SURFACE-ANTIGEN AND ENDONEXIN-II

In a previous study, we have identified endonexin II (E-II) on human liver plasma membranes as a specific, Ca2+-dependent, small hepatitis B surface antigen (HBsAg)-binding protein. In this article, we describe the spontaneous development of anti-HBs antibodies in rabbits immunized with native or recombinant human liver E-II and in chickens immunized with the F(ab')(2) fragment of rabbit anti-human liver E-II immunoglobulin G. Anti-HBs activity was not observed in rabbits immunized with rat liver E-II. Cross-reactivity of anti-E-II antibodies to HBsAg epitopes was excluded, since anti-HBs and anti-E-II activities can be separated by E-II affinity chromatography. The existence of an anti-idiotypic antibody is further demonstrated by competitive binding of human liver E-II and this antibody (Ab2) to small HBsAg, suggesting that Ab2 mimics a specific E-II epitope that interacts with small HBsAg In addition, it was demonstrated that anti-HBs antibodies developed in rabbits after immunization with intact human liver E-II or in chickens after immunization with F(ab')(2) fragments of rabbit anti-human liver E-II immunoglobulin G recognize the same epitopes on small HBsAg. These findings strongly indicate that human liver E-II is a very specific small HBsAg-binding protein and support the assumption that human liver E-II is the hepatitis B virus receptor protein.