Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens.
Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens.
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DOI：
10.1038/srep12411
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发表时间：
2015-07-23
影响因子：
4.6
通讯作者：
Yang AS
中科院分区：
文献类型：
--
作者：
Chen HS;Hou SC;Jian JW;Goh KS;Shen ST;Lee YC;You JJ;Peng HP;Kuo WC;Chen ST;Peng MC;Wang AH;Yu CM;Chen IC;Tung CP;Chen TH;Ping Chiu K;Ma C;Yuan Wu C;Lin SW;Yang AS
针对不同病原体的体液免疫是从有限复杂性的天然抗体库中快速引发的。但是，促进这种免疫的抗体库的组织原则还没有得到很好的理解。我们使用HER2作为模型免疫原，并通过构建人工抗体文库来反向工程化鼠抗体应答，所述人工抗体文库编码有从抗体可变结构域的高通量测序中获得的基本序列和结构特征。从噬菌体展示的合成抗体库中筛选出的抗体与模型免疫原具有高亲和力和特异性结合，重现了天然抗体反应的特异性。我们的结论是，天然抗体结构库的形状，以允许功能性抗体被有效地编码，在一个单独的抗体库的复杂性限制，结合到不同的蛋白质抗原具有高特异性和亲和力。噬菌体展示的合成抗体库，结合高通量测序，因此可以被设计为复制天然抗体反应，并产生针对不同抗原的新抗体。
Humoral immunity against diverse pathogens is rapidly elicited from natural antibody repertoires of limited complexity. But the organizing principles underlying the antibody repertoires that facilitate this immunity are not well-understood. We used HER2 as a model immunogen and reverse-engineered murine antibody response through constructing an artificial antibody library encoded with rudimentary sequence and structural characteristics learned from high throughput sequencing of antibody variable domains. Antibodies selected in vitro from the phage-displayed synthetic antibody library bound to the model immunogen with high affinity and specificities, which reproduced the specificities of natural antibody responses. We conclude that natural antibody structural repertoires are shaped to allow functional antibodies to be encoded efficiently, within the complexity limit of an individual antibody repertoire, to bind to diverse protein antigens with high specificity and affinity. Phage-displayed synthetic antibody libraries, in conjunction with high-throughput sequencing, can thus be designed to replicate natural antibody responses and to generate novel antibodies against diverse antigens.