Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens
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 mu...
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| Veröffentlicht in: | Scientific reports 2015-07, Vol.5 (1), p.12411-12411, Article 12411 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1038/srep12411 |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep12411</identifier><identifier>PMID: 26202883</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Scientific reports, 2015-07, Vol.5 (1), p.12411-12411, Article 12411</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Jul 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-eb814240bf547d7eec88cc088691ef735f1ead1d8a00a6190e5a611f9cb03a863</citedby><cites>FETCH-LOGICAL-c438t-eb814240bf547d7eec88cc088691ef735f1ead1d8a00a6190e5a611f9cb03a863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378893/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378893/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26202883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hong-Sen</creatorcontrib><creatorcontrib>Hou, Shin-Chen</creatorcontrib><creatorcontrib>Jian, Jhih-Wei</creatorcontrib><creatorcontrib>Goh, King-Siang</creatorcontrib><creatorcontrib>Shen, San-Tai</creatorcontrib><creatorcontrib>Lee, Yu-Ching</creatorcontrib><creatorcontrib>You, Jhong-Jhe</creatorcontrib><creatorcontrib>Peng, Hung-Pin</creatorcontrib><creatorcontrib>Kuo, Wen-Chih</creatorcontrib><creatorcontrib>Chen, Shui-Tsung</creatorcontrib><creatorcontrib>Peng, Ming-Chi</creatorcontrib><creatorcontrib>Wang, Andrew H.-J.</creatorcontrib><creatorcontrib>Yu, Chung-Ming</creatorcontrib><creatorcontrib>Chen, Ing-Chien</creatorcontrib><creatorcontrib>Tung, Chao-Ping</creatorcontrib><creatorcontrib>Chen, Tzu-Han</creatorcontrib><creatorcontrib>Ping Chiu, Kuo</creatorcontrib><creatorcontrib>Ma, Che</creatorcontrib><creatorcontrib>Yuan Wu, Chih</creatorcontrib><creatorcontrib>Lin, Sheng-Wei</creatorcontrib><creatorcontrib>Yang, An-Suei</creatorcontrib><title>Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>101/1</subject><subject>45</subject><subject>45/47</subject><subject>49/1</subject><subject>49/23</subject><subject>631/1647/2163</subject><subject>631/1647/514/2254</subject><subject>631/61/338/469</subject><subject>631/92/605</subject><subject>82</subject><subject>82/1</subject><subject>82/47</subject><subject>Affinity</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibody libraries</subject><subject>Antibody response</subject><subject>Antigen-Antibody Reactions - immunology</subject><subject>Antigens</subject><subject>Binding Sites</subject><subject>ErbB-2 protein</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Humoral immunity</subject><subject>Immunity, Innate - immunology</subject><subject>Immunoglobulins</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>multidisciplinary</subject><subject>Next-generation sequencing</subject><subject>Phages</subject><subject>Protein Binding</subject><subject>Receptor, ErbB-2 - chemistry</subject><subject>Receptor, ErbB-2 - immunology</subject><subject>Science</subject><subject>Structure-Activity Relationship</subject><subject>Vaccines</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkU9rFEEQxRuJmBBz8AvIgJcYWO2_s90XIQSTCAE96Lnp6akZO8x2T7p7Ajn51S3dZNloXarg_XhVxSPkDaMfGBX6Y8kwMy4Ze0GOOJVqxQXnB3vzITkp5ZZiKW4kM6_IIW855VqLI_LrW4Y-bUJ0sTal5sXXJbup8SkOYcSxhhSbNDTRbQXkQpf6hwbXQq4pZCgNRNdN2OdUAX32mDKnWFBxowux1GbOiIT4Fxkhltfk5eCmAieP_Zj8uPz8_eJ6dfP16svF-c3KS6HrCjrNJJe0G5Rc92sAr7X3VOvWMBjWQg0MXM967Sh1LTMUFDY2GN9R4XQrjsmnre-8dBvoPZ6J39g5h43LDza5YJ8rMfy0Y7q3Sqy1NgINTh8NcrpboFS7CcXDNLkIaSmWtcZIQynjiL77B71NS474nmXaGEWVZAqp91vK51QwxGF3DKP2T7J2lyyyb_ev35FPOSJwtgUKSnGEvLfyP7ffuLOxtg</recordid><startdate>20150723</startdate><enddate>20150723</enddate><creator>Chen, Hong-Sen</creator><creator>Hou, Shin-Chen</creator><creator>Jian, Jhih-Wei</creator><creator>Goh, King-Siang</creator><creator>Shen, San-Tai</creator><creator>Lee, Yu-Ching</creator><creator>You, Jhong-Jhe</creator><creator>Peng, Hung-Pin</creator><creator>Kuo, Wen-Chih</creator><creator>Chen, Shui-Tsung</creator><creator>Peng, Ming-Chi</creator><creator>Wang, Andrew H.-J.</creator><creator>Yu, Chung-Ming</creator><creator>Chen, Ing-Chien</creator><creator>Tung, Chao-Ping</creator><creator>Chen, Tzu-Han</creator><creator>Ping Chiu, Kuo</creator><creator>Ma, Che</creator><creator>Yuan Wu, Chih</creator><creator>Lin, Sheng-Wei</creator><creator>Yang, An-Suei</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150723</creationdate><title>Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-eb814240bf547d7eec88cc088691ef735f1ead1d8a00a6190e5a611f9cb03a863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>101/1</topic><topic>45</topic><topic>45/47</topic><topic>49/1</topic><topic>49/23</topic><topic>631/1647/2163</topic><topic>631/1647/514/2254</topic><topic>631/61/338/469</topic><topic>631/92/605</topic><topic>82</topic><topic>82/1</topic><topic>82/47</topic><topic>Affinity</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibody libraries</topic><topic>Antibody response</topic><topic>Antigen-Antibody Reactions - immunology</topic><topic>Antigens</topic><topic>Binding Sites</topic><topic>ErbB-2 protein</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Humoral immunity</topic><topic>Immunity, Innate - immunology</topic><topic>Immunoglobulins</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>multidisciplinary</topic><topic>Next-generation sequencing</topic><topic>Phages</topic><topic>Protein Binding</topic><topic>Receptor, ErbB-2 - chemistry</topic><topic>Receptor, ErbB-2 - immunology</topic><topic>Science</topic><topic>Structure-Activity Relationship</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hong-Sen</creatorcontrib><creatorcontrib>Hou, Shin-Chen</creatorcontrib><creatorcontrib>Jian, Jhih-Wei</creatorcontrib><creatorcontrib>Goh, King-Siang</creatorcontrib><creatorcontrib>Shen, San-Tai</creatorcontrib><creatorcontrib>Lee, Yu-Ching</creatorcontrib><creatorcontrib>You, Jhong-Jhe</creatorcontrib><creatorcontrib>Peng, Hung-Pin</creatorcontrib><creatorcontrib>Kuo, Wen-Chih</creatorcontrib><creatorcontrib>Chen, Shui-Tsung</creatorcontrib><creatorcontrib>Peng, Ming-Chi</creatorcontrib><creatorcontrib>Wang, Andrew H.-J.</creatorcontrib><creatorcontrib>Yu, Chung-Ming</creatorcontrib><creatorcontrib>Chen, Ing-Chien</creatorcontrib><creatorcontrib>Tung, Chao-Ping</creatorcontrib><creatorcontrib>Chen, Tzu-Han</creatorcontrib><creatorcontrib>Ping Chiu, Kuo</creatorcontrib><creatorcontrib>Ma, Che</creatorcontrib><creatorcontrib>Yuan Wu, Chih</creatorcontrib><creatorcontrib>Lin, Sheng-Wei</creatorcontrib><creatorcontrib>Yang, An-Suei</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hong-Sen</au><au>Hou, Shin-Chen</au><au>Jian, Jhih-Wei</au><au>Goh, King-Siang</au><au>Shen, San-Tai</au><au>Lee, Yu-Ching</au><au>You, Jhong-Jhe</au><au>Peng, Hung-Pin</au><au>Kuo, Wen-Chih</au><au>Chen, Shui-Tsung</au><au>Peng, Ming-Chi</au><au>Wang, Andrew H.-J.</au><au>Yu, Chung-Ming</au><au>Chen, Ing-Chien</au><au>Tung, Chao-Ping</au><au>Chen, Tzu-Han</au><au>Ping Chiu, Kuo</au><au>Ma, Che</au><au>Yuan Wu, Chih</au><au>Lin, Sheng-Wei</au><au>Yang, An-Suei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-07-23</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>12411</spage><epage>12411</epage><pages>12411-12411</pages><artnum>12411</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26202883</pmid><doi>10.1038/srep12411</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens |
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