Characterization of small hepatitis B surface antigen epitopes involved inbinding to human annexin V

Previously, we have shown that small hepatitis B surface antigen (SHBsAg) b inds 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 demon strated the spontaneous development of anti-idiotypic antibodies (antibodie s to HBsAg Ab2) in rabbits immunized with hAV; As Ab2 is able to inhibit th e binding of hAV to SHBsAg, Ab2 might contain epitope(s) mimicking a region of hAV for binding to SHBsAg, Identification of this epitope will therefor e reveal a SHBsAg sequence involved in hAV binding. Using a panel of synthe tic 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 al so for binding to hAV. Further experiments revealed that not only this regi on, but also the region incorporating aa 158-169, is involved in the bindin g 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 f indings 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 infec tion, further studies on the HBsAg epitopes for hAV binding may lead to the development of a new generation of vaccines or molecules for prevention an d for treatment of patients with chronic hepatitis B.