Spontaneous development of anti-hepatitis B virus envelope (anti-idiotypic) 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, Ca(2+)-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.
Hertogs
K
K
Division of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Leuven, Belgium.
Depla
E
E
Crabbé
T
T
De Bruin
W
W
Leenders
W
W
Moshage
H
H
Yap
S H
SH
D000818:Animals; D017304:Annexin A5 / Q000276:immunology*; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D001667:Binding, Competitive; D002645:Chickens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007114:Immunization; D015151:Immunoblotting; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008099:Liver / Q000276:immunology; D011233:Precipitin Tests; D011817:Rabbits / Q000276:immunology; D011946:Receptors, Antigen / Q000276:immunology
D017304:Annexin A5; D000888:Antibodies, Anti-Idiotypic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011946:Receptors, Antigen; C030500:hepatitis B surface antigen receptor