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 Lin; An Suei Yang

doi:10.1038/srep12411

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

Research output: Contribution to journal › Article › peer-review

18 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 language	English
Article number	12411
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep12411
Publication status	Published - Jul 23 2015
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1038/srep12411

Cite this

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, Article 12411. https://doi.org/10.1038/srep12411

Chen, HS, Hou, SC, Jian, JW, Goh, KS, Shen, ST, Lee, YC, You, JJ, Peng, HP, Kuo, WC, Chen, ST, Peng, MC, Wang, AHJ, Yu, CM, Chen, IC, Tung, CP, Chen, TH, Ping Chiu, K, Ma, C, Yuan Wu, C, Lin, SW & Yang, AS 2015, 'Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens', Scientific Reports, vol. 5, 12411. https://doi.org/10.1038/srep12411

@article{7125e7386d2e43c28a535406b3cd9e6f,

title = "Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens",

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.",

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

note = "Funding Information: We would like to thank the support of the research projects 103-2622-B-001-001-CC2 and 103-2325-B-001-023 from Ministry of Science and Technology (MoST) in Taiwan, and support of postdoctoral position (S-T Shen) under the project 103-2811-B-001-006 from MoST. This research was also supported by Academia Sinica and MoST [104-0210-01-09-02]. We would like to thank Dr. Peter Kwong of NIH for helpful discussion and Dr. Todd Juan of JHL biotech Inc. for collaboration in IgG production and characterization.",

year = "2015",

month = jul,

day = "23",

doi = "10.1038/srep12411",

language = "English",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

}

TY - JOUR

T1 - Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens

AU - Chen, Hong Sen

AU - Hou, Shin Chen

AU - Jian, Jhih Wei

AU - Goh, King Siang

AU - Shen, San Tai

AU - Lee, Yu Ching

AU - You, Jhong Jhe

AU - Peng, Hung Pin

AU - Kuo, Wen Chih

AU - Chen, Shui Tsung

AU - Peng, Ming Chi

AU - Wang, Andrew H.J.

AU - Yu, Chung Ming

AU - Chen, Ing Chien

AU - Tung, Chao Ping

AU - Chen, Tzu Han

AU - Ping Chiu, Kuo

AU - Ma, Che

AU - Yuan Wu, Chih

AU - Lin, Sheng Wei

AU - Yang, An Suei

N1 - Funding Information: We would like to thank the support of the research projects 103-2622-B-001-001-CC2 and 103-2325-B-001-023 from Ministry of Science and Technology (MoST) in Taiwan, and support of postdoctoral position (S-T Shen) under the project 103-2811-B-001-006 from MoST. This research was also supported by Academia Sinica and MoST [104-0210-01-09-02]. We would like to thank Dr. Peter Kwong of NIH for helpful discussion and Dr. Todd Juan of JHL biotech Inc. for collaboration in IgG production and characterization.

PY - 2015/7/23

Y1 - 2015/7/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84937876252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937876252&partnerID=8YFLogxK

U2 - 10.1038/srep12411

DO - 10.1038/srep12411

M3 - Article

C2 - 26202883

AN - SCOPUS:84937876252

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 12411

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this