Predominant Structural Configuration of Natural Antibody Repertoires Enables Potent Antibody Responses Against Protein Antigens

Overview

Journal Sci Rep

Specialty Science

Date 2015 Jul 24

PMID 26202883

Citations 13

Authors

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

Affiliations

Soon will be listed here.

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.

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