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.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Hong-Sen
authors.initials: HS
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Shin-Chen
authors.initials: SC
authors.lastname: Hou
authors.affiliation: 1] Genomics Research Center, Academia Sinica, Taipei, Taiwan 115 [2] Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan 112 [3] Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Jhih-Wei
authors.initials: JW
authors.lastname: Jian
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: King-Siang
authors.initials: KS
authors.lastname: Goh
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: San-Tai
authors.initials: ST
authors.lastname: Shen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Jhong-Jhe
authors.initials: JJ
authors.lastname: You
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Hung-Pin
authors.initials: HP
authors.lastname: Peng
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Wen-Chih
authors.initials: WC
authors.lastname: Kuo
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Shui-Tsung
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Peng
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Yu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Ing-Chien
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Tung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Tzu-Han
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Kuo
authors.initials: K
authors.lastname: Ping Chiu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Che
authors.initials: C
authors.lastname: Ma
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Chih
authors.initials: C
authors.lastname: Yuan Wu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: An-Suei
authors.initials: AS
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D001665:Binding Sites; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human