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

• Published in: Scientific reports Vol. 5; no. 1; p. 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.07.2015; Nature Publishing Group
• Subjects: 101/1; 45; 45/47; 49/1; 49/23; 631/1647/2163; 631/1647/514/2254; 631/61/338/469; 631/92/605; 82; 82/1; 82/47; Affinity; Amino Acid Sequence; Animals; Antibodies; Antibody libraries; Antibody response; Antigen-Antibody Reactions - immunology; Antigens; Binding Sites; ErbB-2 protein; Humanities and Social Sciences; Humans; Humoral immunity; Immunity, Innate - immunology; Immunoglobulins; Mice; Molecular Sequence Data; multidisciplinary; Next-generation sequencing; Phages; Protein Binding; Receptor, ErbB-2 - chemistry; Receptor, ErbB-2 - immunology; Science; Structure-Activity Relationship; Vaccines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep12411

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.