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阻断抗体在肉毒神经毒素 A 轻链上的识别区域:整个毒素的抗原结构。

Regions of recognition by blocking antibodies on the light chain of botulinum neurotoxin A: antigenic structure of the entire toxin.

机构信息

Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Immunobiology. 2011 Jun;216(6):698-706. doi: 10.1016/j.imbio.2010.10.010. Epub 2010 Nov 4.

DOI:10.1016/j.imbio.2010.10.010
PMID:21183243
Abstract

The continuous regions on botulinum neurotoxin A (BoNT/A) light (L) chain recognized by anti-toxin antibodies (Abs) from mouse, horse and chicken have been mapped. We synthesized a panel of thirty-two 19-residue peptides that overlapped consecutively by 5 residues and encompassed the entire L chain (residues 1-453). Mouse Abs recognized 5 major antigenic regions on the L chain, horse Abs recognized 9 while chicken Abs recognized 8 major antigenic regions. Overall, however, the three host species recognized, to some extent, similar, but not identical, peptides and the levels of Abs directed against a given region varied with the immunized host. Differences in the MHC of the host caused variation in levels of Ab recognition and some epitopes showed right or left frame-shifts among the species. Selected region(s) were also uniquely recognized by one species (e.g., peptide L1 by horse Abs). Mapping of the L chain antigenic regions and the previous localization of the regions on the H chain with the same antisera, has permitted description of the complete antigenic structure of BoNT/A. The locations in the 3-dimensional structure of the antigenic regions of the entire toxin are shown for mouse Abs. In the 3-D structure, the antigenic regions are on the surface of the toxin and when antibodies are bound the enzymatic activity of the light chain is obstructed.

摘要

抗毒素抗体(Abs)识别的肉毒神经毒素 A(BoNT/A)轻链(L)连续区域已被定位。我们合成了一组由 32 个 19 个残基组成的肽,这些肽通过 5 个残基连续重叠,涵盖了整个 L 链(残基 1-453)。鼠 Abs 识别 L 链上的 5 个主要抗原区域,马 Abs 识别 9 个,而鸡 Abs 识别 8 个主要抗原区域。然而,总的来说,这三种宿主物种在某种程度上识别出相似但不相同的肽,并且针对特定区域的 Abs 水平因免疫宿主而异。宿主 MHC 的差异导致 Abs 识别水平的变化,并且一些表位在物种之间显示出右或左移框。选定的区域也被一种物种(例如,马 Abs 识别的肽 L1)特异性识别。L 链抗原区域的定位以及用相同抗血清对 H 链上的相同区域的定位,使得能够描述 BoNT/A 的完整抗原结构。显示了针对鼠 Abs 的整个毒素抗原区域的三维结构中的位置。在三维结构中,抗原区域位于毒素的表面,当抗体结合时,轻链的酶活性受到阻碍。

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