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

Hong Sen Chen, Shin Chen Hou, Jhih Wei Jian, King Siang Goh, San Tai Shen, Yu Ching Lee, Jhong Jhe You, Hung Pin Peng, Wen Chih Kuo, Shui Tsung Chen, Ming Chi Peng, Andrew H.J. Wang, Chung Ming Yu, Ing Chien Chen, Chao Ping Tung, Tzu Han Chen, Kuo Ping Chiu, Che Ma, Chih Yuan Wu, Sheng Wei LinAn Suei Yang

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8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number12411
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Jul 23 2015
Externally publishedYes

ASJC Scopus subject areas

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    Chen, H. S., Hou, S. C., Jian, J. W., Goh, K. S., Shen, S. T., Lee, Y. C., You, J. J., Peng, H. P., Kuo, W. C., Chen, S. T., Peng, M. C., Wang, A. H. J., Yu, C. M., Chen, I. C., Tung, C. P., Chen, T. H., Ping Chiu, K., Ma, C., Yuan Wu, C., ... Yang, A. S. (2015). Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens. Scientific Reports, 5, [12411]. https://doi.org/10.1038/srep12411