Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens

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 mu...

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Bibliographic Details
Published in:Scientific reports 2015-07, Vol.5 (1), p.12411-12411, Article 12411
Main Authors: Chen, Hong-Sen, Hou, Shin-Chen, Jian, Jhih-Wei, Goh, King-Siang, Shen, San-Tai, Lee, Yu-Ching, You, Jhong-Jhe, Peng, Hung-Pin, Kuo, Wen-Chih, Chen, Shui-Tsung, Peng, Ming-Chi, Wang, Andrew H-J, Yu, Chung-Ming, Chen, Ing-Chien, Tung, Chao-Ping, Chen, Tzu-Han, Ping Chiu, Kuo, Ma, Che, Yuan Wu, Chih, Lin, Sheng-Wei, Yang, An-Suei
Format: Article
Language:English
Subjects:
Affinity
Amino Acid Sequence
Animals
Antibodies
Antibody libraries
Antibody response
Antigen-Antibody Reactions - immunology
Antigens
Binding Sites
ErbB-2 protein
Humans
Humoral immunity
Immunity, Innate - immunology
Immunoglobulins
Mice
Molecular Sequence Data
Next-generation sequencing
Phages
Protein Binding
Receptor, ErbB-2 - chemistry
Receptor, ErbB-2 - immunology
Structure-Activity Relationship
Vaccines
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep12411