Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens
| Autor: | Kuo Ping Chiu, San Tai Shen, Chung Ming Yu, Sheng-Wei Lin, Ming Chi Peng, Shui Tsung Chen, An-Suei Yang, Shin-Chen Hou, King Siang Goh, Hung-Pin Peng, Chao Ping Tung, Jhong Jhe You, Andrew H.-J. Wang, Yu Ching Lee, Tzu Han Chen, Chih Yuan Wu, Hong Sen Chen, Wen Chih Kuo, Jhih-Wei Jian, Ing Chien Chen, Che Ma |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Binding Sites
Multidisciplinary Immunogen Receptor ErbB-2 Molecular Sequence Data Computational biology Biology Virology Immunity Innate Article Synthetic antibody Antigen-Antibody Reactions Mice Structure-Activity Relationship Antibody Repertoire Antigen Immunity Humoral immunity biology.protein Animals Humans Amino Acid Sequence Antibody Binding site Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep12411 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|