Characterization of small hepatitis B surface antigen epitopes involved in binding to human annexin V.
Previously, we have shown that small hepatitis B surface antigen (SHBsAg) binds specifically to human annexin V (hAV) and that hAV plays a key role in the initial steps of hepatitis B virus (HBV) infection. We have also demonstrated the spontaneous development of anti-idiotypic antibodies (antibodies to HBsAg Ab2) in rabbits immunized with hAV. As Ab2 is able to inhibit the binding of hAV to SHBsAg, Ab2 might contain epitope(s) mimicking a region of hAV for binding to SHBsAg. Identification of this epitope will therefore reveal a SHBsAg sequence involved in hAV binding. Using a panel of synthetic peptides covering the region of SHBsAg located on the outer surface of the virus, binding studies showed that the region incorporating amino acids (aa) 125-131 of SHBsAg is important for binding to Ab2 and consequently also for binding to hAV. Further experiments revealed that not only this region, but also the region incorporating aa 158-169, is involved in the binding of SHBsAg to hAV. As these regions are located in the structural vicinity according to the topological model of HBsAg proposed by Chen et al., our findings suggest that these regions are parts of a conformational epitope of SHBsAg for binding to hAV. Because of the crucial role of hAV in HBV infection, further studies on the HBsAg epitopes for hAV binding may lead to the development of a new generation of vaccines or molecules for prevention and for treatment of patients with chronic hepatitis B.
De Meyer
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Department of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Catholic University Leuven, Belgium.
Depla
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E
Maertens
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G
Soumillion
A
A
Yap
S H
SH
D000595:Amino Acid Sequence; D000818:Animals; D017304:Annexin A5 / Q000276:immunology / Q000378:metabolism*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000378:metabolism; D018604:Epitope Mapping; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins
D017304:Annexin A5; D000888:Antibodies, Anti-Idiotypic; D006514:Hepatitis B Surface Antigens; D010455:Peptides; D011994:Recombinant Proteins