Germline antibody recognition of distinct carbohydrate epitopes
Germline antibody recognition of distinct carbohydrate epitopes
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DOI：
10.1038/nsb1014
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发表时间：
2003-12-01
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影响因子：
--
通讯作者：
Evans, SV
中科院分区：
文献类型：
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作者：
Nguyen, HP;Seto, NOL;Evans, SV
高分辨率结构揭示了种系抗体如何识别一系列临床相关的碳水化合物表位。对碳水化合物免疫原的种系反应对存活率至关重要，选择抗体基因片段，既能保护免受常见病原体的侵害，又能保持适应新疾病生物体的灵活性。我们在这里显示，抗体S25-2通过将遗传的单糖残基结合位点与定位为识别不同表位阵列的其余部分的有限灵活性的互补决定区（CDR）的子集连接来结合细菌脂多糖（LPS）的几个不同的内核表位。这种策略允许种系抗体适应不同的表位，同时最小化与抗原结合后不稳定CDR的固定相关的熵罚分，并提供了对单个CDR的遗传起源与其各自在抗原识别中的作用之间的联系的洞察。
High-resolution structures reveal how a germline antibody can recognize a range of clinically relevant carbohydrate epitopes. The germline response to a carbohydrate immunogen can be critical to survivability, with selection for antibody gene segments that both confer protection against common pathogens and retain the flexibility to adapt to new disease organisms. We show here that antibody S25-2 binds several distinct inner-core epitopes of bacterial lipopolysaccharides (LPSs) by linking an inherited monosaccharide residue binding site with a subset of complementarity-determining regions (CDRs) of limited flexibility positioned to recognize the remainder of an array of different epitopes. This strategy allows germline antibodies to adapt to different epitopes while minimizing entropic penalties associated with the immobilization of labile CDRs upon binding of antigen, and provides insight into the link between the genetic origin of individual CDRs and their respective roles in antigen recognition.