Immortalization and functional screening of natively paired human T cell receptor repertoires
Abstract Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major...
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| Veröffentlicht in: | Protein engineering, design and selection design and selection, 2022-02, Vol.35 |
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| creator | Fahad, Ahmed S Chung, Cheng-Yu Lopez Acevedo, Sheila N Boyle, Nicoleen Madan, Bharat Gutiérrez-González, Matias F Matus-Nicodemos, Rodrigo Laflin, Amy D Ladi, Rukmini R Zhou, John Wolfe, Jacy Llewellyn-Lacey, Sian Koup, Richard A Douek, Daniel C Balfour Jr, Henry H Price, David A DeKosky, Brandon J |
| description | Abstract
Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. We developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale, and to exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of disease-relevant antigen interactions with human TCRs. |
| doi_str_mv | 10.1093/protein/gzab034 |
| format | Article |
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Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. We developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale, and to exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of disease-relevant antigen interactions with human TCRs.</description><identifier>ISSN: 1741-0126</identifier><identifier>EISSN: 1741-0134</identifier><identifier>DOI: 10.1093/protein/gzab034</identifier><identifier>PMID: 35174859</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Antigens ; Humans ; Original ; Peptides - chemistry ; Receptors, Antigen, T-Cell - chemistry ; Receptors, Antigen, T-Cell, alpha-beta - genetics</subject><ispartof>Protein engineering, design and selection, 2022-02, Vol.35</ispartof><rights>The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-22b344cd10da7140620ff9a4f32ae927da4f9f5f9cdaa03f287ea677fa342c273</citedby><cites>FETCH-LOGICAL-c428t-22b344cd10da7140620ff9a4f32ae927da4f9f5f9cdaa03f287ea677fa342c273</cites><orcidid>0000-0001-6406-0836 ; 0000-0002-5088-9333</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35174859$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fahad, Ahmed S</creatorcontrib><creatorcontrib>Chung, Cheng-Yu</creatorcontrib><creatorcontrib>Lopez Acevedo, Sheila N</creatorcontrib><creatorcontrib>Boyle, Nicoleen</creatorcontrib><creatorcontrib>Madan, Bharat</creatorcontrib><creatorcontrib>Gutiérrez-González, Matias F</creatorcontrib><creatorcontrib>Matus-Nicodemos, Rodrigo</creatorcontrib><creatorcontrib>Laflin, Amy D</creatorcontrib><creatorcontrib>Ladi, Rukmini R</creatorcontrib><creatorcontrib>Zhou, John</creatorcontrib><creatorcontrib>Wolfe, Jacy</creatorcontrib><creatorcontrib>Llewellyn-Lacey, Sian</creatorcontrib><creatorcontrib>Koup, Richard A</creatorcontrib><creatorcontrib>Douek, Daniel C</creatorcontrib><creatorcontrib>Balfour Jr, Henry H</creatorcontrib><creatorcontrib>Price, David A</creatorcontrib><creatorcontrib>DeKosky, Brandon J</creatorcontrib><title>Immortalization and functional screening of natively paired human T cell receptor repertoires</title><title>Protein engineering, design and selection</title><addtitle>Protein Eng Des Sel</addtitle><description>Abstract
Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. We developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale, and to exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of disease-relevant antigen interactions with human TCRs.</description><subject>Antigens</subject><subject>Humans</subject><subject>Original</subject><subject>Peptides - chemistry</subject><subject>Receptors, Antigen, T-Cell - chemistry</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - genetics</subject><issn>1741-0126</issn><issn>1741-0134</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1LXDEUxUOp1I923V3JshTGydf7yEYQaasguNGlhDt5N2PKe8kzeU_Qv94MMx105eqey_nlJOEQ8p2zU860XI4pTujDcv0CKybVJ3LEG8UXjEv1ea9FfUiOc_7HmKgbzr-QQ1kVq630Ebm_GoaYJuj9C0w-Bgqho24OdrNAT7NNiMGHNY2OhoI8Yf9MR_AJO_owDxDoLbXY9zShxXGKqYgR0xQLkb-SAwd9xm-7eULu_vy-vbhcXN_8vbo4v15YJdppIcRKKmU7zjpouGK1YM5pUE4KQC2arkjtKqdtB8CkE22DUDeNA6mEFY08IWfb3HFeDdhZDFOC3ozJD5CeTQRv3jvBP5h1fDKasYpVsgT83AWk-Dhjnszg8-ZbEDDO2Yha6LZqtagKutyiNsWcE7r9NZyZTSlmV4rZlVJO_Hj7uj3_v4UC_NoCcR4_THsFJkmdcw</recordid><startdate>20220217</startdate><enddate>20220217</enddate><creator>Fahad, Ahmed S</creator><creator>Chung, Cheng-Yu</creator><creator>Lopez Acevedo, Sheila N</creator><creator>Boyle, Nicoleen</creator><creator>Madan, Bharat</creator><creator>Gutiérrez-González, Matias F</creator><creator>Matus-Nicodemos, Rodrigo</creator><creator>Laflin, Amy D</creator><creator>Ladi, Rukmini R</creator><creator>Zhou, John</creator><creator>Wolfe, Jacy</creator><creator>Llewellyn-Lacey, Sian</creator><creator>Koup, Richard A</creator><creator>Douek, Daniel C</creator><creator>Balfour Jr, Henry H</creator><creator>Price, David A</creator><creator>DeKosky, Brandon J</creator><general>Oxford University Press</general><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6406-0836</orcidid><orcidid>https://orcid.org/0000-0002-5088-9333</orcidid></search><sort><creationdate>20220217</creationdate><title>Immortalization and functional screening of natively paired human T cell receptor repertoires</title><author>Fahad, Ahmed S ; Chung, Cheng-Yu ; Lopez Acevedo, Sheila N ; Boyle, Nicoleen ; Madan, Bharat ; Gutiérrez-González, Matias F ; Matus-Nicodemos, Rodrigo ; Laflin, Amy D ; Ladi, Rukmini R ; Zhou, John ; Wolfe, Jacy ; Llewellyn-Lacey, Sian ; Koup, Richard A ; Douek, Daniel C ; Balfour Jr, Henry H ; Price, David A ; DeKosky, Brandon J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-22b344cd10da7140620ff9a4f32ae927da4f9f5f9cdaa03f287ea677fa342c273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antigens</topic><topic>Humans</topic><topic>Original</topic><topic>Peptides - chemistry</topic><topic>Receptors, Antigen, T-Cell - chemistry</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fahad, Ahmed S</creatorcontrib><creatorcontrib>Chung, Cheng-Yu</creatorcontrib><creatorcontrib>Lopez Acevedo, Sheila N</creatorcontrib><creatorcontrib>Boyle, Nicoleen</creatorcontrib><creatorcontrib>Madan, Bharat</creatorcontrib><creatorcontrib>Gutiérrez-González, Matias F</creatorcontrib><creatorcontrib>Matus-Nicodemos, Rodrigo</creatorcontrib><creatorcontrib>Laflin, Amy D</creatorcontrib><creatorcontrib>Ladi, Rukmini R</creatorcontrib><creatorcontrib>Zhou, John</creatorcontrib><creatorcontrib>Wolfe, Jacy</creatorcontrib><creatorcontrib>Llewellyn-Lacey, Sian</creatorcontrib><creatorcontrib>Koup, Richard A</creatorcontrib><creatorcontrib>Douek, Daniel C</creatorcontrib><creatorcontrib>Balfour Jr, Henry H</creatorcontrib><creatorcontrib>Price, David A</creatorcontrib><creatorcontrib>DeKosky, Brandon J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Protein engineering, design and selection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fahad, Ahmed S</au><au>Chung, Cheng-Yu</au><au>Lopez Acevedo, Sheila N</au><au>Boyle, Nicoleen</au><au>Madan, Bharat</au><au>Gutiérrez-González, Matias F</au><au>Matus-Nicodemos, Rodrigo</au><au>Laflin, Amy D</au><au>Ladi, Rukmini R</au><au>Zhou, John</au><au>Wolfe, Jacy</au><au>Llewellyn-Lacey, Sian</au><au>Koup, Richard A</au><au>Douek, Daniel C</au><au>Balfour Jr, Henry H</au><au>Price, David A</au><au>DeKosky, Brandon J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immortalization and functional screening of natively paired human T cell receptor repertoires</atitle><jtitle>Protein engineering, design and selection</jtitle><addtitle>Protein Eng Des Sel</addtitle><date>2022-02-17</date><risdate>2022</risdate><volume>35</volume><issn>1741-0126</issn><eissn>1741-0134</eissn><abstract>Abstract
Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. We developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale, and to exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of disease-relevant antigen interactions with human TCRs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35174859</pmid><doi>10.1093/protein/gzab034</doi><orcidid>https://orcid.org/0000-0001-6406-0836</orcidid><orcidid>https://orcid.org/0000-0002-5088-9333</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antigens Humans Original Peptides - chemistry Receptors, Antigen, T-Cell - chemistry Receptors, Antigen, T-Cell, alpha-beta - genetics |
| title | Immortalization and functional screening of natively paired human T cell receptor repertoires |
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