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首页> 外文期刊>Journal of Molecular Biology >Molecular basis for the high degree of antigenic cross-reactivity between hepatitis B virus capsids (HBcAg) and dimeric capsid-related protein (HBeAg): insights into the enigmatic nature of the e-antigen.
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Molecular basis for the high degree of antigenic cross-reactivity between hepatitis B virus capsids (HBcAg) and dimeric capsid-related protein (HBeAg): insights into the enigmatic nature of the e-antigen.

机译：乙型肝炎病毒衣壳（HBcAg）与二聚体衣壳相关蛋白（HBeAg）之间高度抗原性交叉反应的分子基础：对电子抗原的神秘性质的见解。

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The hepatitis B virus core gene codes for two closely related antigens: a 21-kDa protein that forms dimers that assemble as multimegadalton capsids, and a 17-kDa protein that also forms dimers but that do not assemble. The proteins, respectively referred to as core antigen (HBcAg) and e-antigen (HBeAg), share a sequence of 149 residues but have different amino- and carboxy-termini. Their structural and serological relationship has long been unclear. With insights gained from recent structural studies on immune complexes of the capsids, the relationship was reassessed using recombinant forms of the antigens and a panel of monoclonal antibodies (mAbs) commonly believed to discriminate between core and e-antigen. Surface plasmon resonance (SPR) was used to measure the affinities, in contrast to previous studies that used more error-prone and less sensitive plate-type assays. Four of the six mAbs did not discriminate between core and e-antigen, nor did they discriminate between e-antigen and dimers of dissociated core antigen capsids. One mAb (3120) was specific for assembled capsids and one (e6) was specific for unassembled dimers. Epitope valency of the e-antigen was also studied, using a sandwich SPR assay where e-antigen was captured with one mAb and probed with a second. The e-antigen is often considered to be a monomeric protein on the basis of monovalent reactivity with antibody pairs specific for either an alpha or beta epitope (in a prior nomenclature for e-antigen specificity). This model, however, is incorrect, because recombinant e-antigen is a stable dimer and its apparent monovalency is due to steric blockage. This was proven by the formation of a 2:1 Fab e6-e-antigen complex. These results suggest new approaches for the isolation of the authentic e-antigen, its biological assay, and its stabilization as an immune complex for structural studies.
机译：乙型肝炎病毒核心基因编码两个密切相关的抗原：一个21-kDa的蛋白质形成二聚体，装配成多兆达级衣壳;另一个17-kDa的蛋白质也形成二聚体但不装配。这些蛋白分别称为核心抗原（HBcAg）和电子抗原（HBeAg），共有149个残基序列，但具有不同的氨基和羧基末端。它们的结构和血清学关系一直不清楚。从最近对衣壳免疫复合物的结构研究中获得的见识，使用重组形式的抗原和通常被认为能够区分核心抗原和电子抗原的一组单克隆抗体（mAb），重新评估了这种关系。与以前的研究相比，表面等离振子共振（SPR）用于测量亲和力，以前的研究使用了更多的容易出错和较不敏感的板型检测方法。六个mAb中有四个不能区分核心抗原和e-抗原，也不能区分电子抗原和解离的核心抗原衣壳的二聚体。一种mAb（3120）专用于组装的衣壳，一种（e6）专用于未组装的二聚体。还使用夹心SPR分析法研究了e-抗原的表位价，其中用一种mAb捕获e-抗原并用第二种mAb进行探测。基于与对α或β表位具有特异性的抗体对的单价反应性，e抗原通常被认为是单体蛋白（在先前的术语中为e抗原特异性）。但是，此模型是不正确的，因为重组e-抗原是稳定的二聚体，其表观单价性是由于位阻。通过形成2：1 Fab e6-e-抗原复合物证明了这一点。这些结果提出了分离真实电子抗原，对其生物学测定以及将其稳定为结构研究的免疫复合物的新方法。

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