Diversity of core antigen epitopes of hepatitis B virus
Diversity of core antigen epitopes of hepatitis B virus
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DOI：
10.1073/pnas.1834404100
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发表时间：
2003-09-16
影响因子：
11.1
通讯作者：
Steven, AC
中科院分区：
文献类型：
--
作者：
Belnap, DM;Watts, NR;Steven, AC
核心抗原（cAg），即病毒衣壳，是乙型肝炎病毒临床三大抗原之一。 cAg 被描述为呈现一个或两个涉及“免疫显性环”的构象表位。我们通过冷冻电子显微镜以大约 11 埃的分辨率研究了单克隆 Fab 标记的衣壳的 cAg 抗原性，并结合分子建模，并在此描述了两种构象表位。两个 Fab 均与二聚体外部刺突结合，并且每个表位都有来自两个亚基上环的贡献，这解释了它们的不连续性质：然而，它们的结合方面和表位显着不同。迄今为止，四个 cAg 表位已得到表征：全部都是不同的。尽管衣壳表面只有两个区域可供抗体接触，但有限数量的暴露肽环的局部聚集会产生一组潜在的广泛的不连续表位。由于空间干扰效应，这种多样性在竞争实验中并不明显。这些观察结果提出了对 cAg 和 e 抗原（衣壳蛋白的未组装形式）之间区别的解释，以及利用 cAg 表位多样性的免疫诊断方法。
Core antigen (cAg), the viral capsid, is one of the three major clinical antigens of hepatitis B virus. cAg has been described as presenting either one or two conformational epitopes involving the "immunodominant loop." We have investigated cAg antigenicity by cryo-electron microscopy at approximate to11-Angstrom resolution of capsids labeled with monoclonal Fabs, combined with molecular modeling, and describe here two conformational epitopes. Both Fabs bind to the dimeric external spikes, and each epitope has contributions from the loops on both subunits, explaining their discontinuous nature: however, their binding aspects and epitopes differ markedly. To date, four cAg epitopes have been characterized: all are distinct. Although only two regions of the capsid surface are accessible to antibodies, local clustering of the limited number of exposed peptide loops generates a potentially extensive set of discontinuous epitopes. This diversity has not been evident from competition experiments because of steric interference effects. These observations suggest an explanation for the distinction between cAg and e-antigen (an unassembled form of capsid protein) and an approach to immunodiagnosis, exploiting the diversity of cAg epitopes.