TCR Repertoire Analysis by Next Generation Sequencing Allows Complex Differential Diagnosis of T Cell–Related Pathology
Clonotype analysis is essential for complete characterization of antigen‐specific T cells. Moreover, knowledge on clonal identity allows tracking of antigen‐specific T cells in whole blood and tissue infiltrates and can provide information on antigenic specificity. Here, we developed a next generati...
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| Veröffentlicht in: | American journal of transplantation 2013-11, Vol.13 (11), p.2842-2854 |
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| creator | Dziubianau, M. Hecht, J. Kuchenbecker, L. Sattler, A. Stervbo, U. Rödelsperger, C. Nickel, P. Neumann, A. U. Robinson, P. N. Mundlos, S. Volk, H.‐D. Thiel, A. Reinke, P. Babel, N. |
| description | Clonotype analysis is essential for complete characterization of antigen‐specific T cells. Moreover, knowledge on clonal identity allows tracking of antigen‐specific T cells in whole blood and tissue infiltrates and can provide information on antigenic specificity. Here, we developed a next generation sequencing (NGS)‐based platform for the highly quantitative clonotype characterization of T cells and determined requirements for the unbiased characterization of the input material (DNA, RNA, ex vivo derived or cell culture expanded T cells). Thereafter we performed T cell receptor (TCR) repertoire analysis of various specimens in clinical settings including cytomegalovirus (CMV), polyomavirus BK (BKV) reactivation and acute cellular allograft rejection. Our results revealed dynamic nature of virus‐specific T cell clonotypes; CMV reactivation was linked to appearance of new highly abundant antigen‐specific clonalities. Moreover, analysis of clonotype overlap between BKV‐, alloantigen‐specific T cell–, kidney allograft‐ and urine‐derived lymphocytes provided hints for the differential diagnosis of allograft dysfunction and enabled appropriate therapy adjustment. We believe that the established approach will provide insights into the regulation of virus‐specific/anti‐tumor immunity and has high diagnostic potential in the clinical routine.
This study describes the development and characterization of T cell receptor repertoire analysis based on Next Generation Sequencing and its application for complex differential diagnosis of posttransplant kidney dysfunction. |
| doi_str_mv | 10.1111/ajt.12431 |
| format | Article |
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This study describes the development and characterization of T cell receptor repertoire analysis based on Next Generation Sequencing and its application for complex differential diagnosis of posttransplant kidney dysfunction.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.12431</identifier><identifier>PMID: 24020931</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley</publisher><subject>Acute cellular rejection ; Biological and medical sciences ; BK Virus - genetics ; BKV ; Blood ; Cytomegalovirus ; Cytomegalovirus - immunology ; Cytomegalovirus - pathogenicity ; Cytomegalovirus Infections - diagnosis ; Cytomegalovirus Infections - genetics ; Cytomegalovirus Infections - virology ; Diagnosis, Differential ; differential diagnosis ; Graft Rejection - genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunology ; kidney transplantation ; Kidney Transplantation - adverse effects ; Lymphocytes ; Medical sciences ; next generation sequencing ; Pathology ; polyoma ; Polyomavirus Infections - diagnosis ; Polyomavirus Infections - genetics ; Polyomavirus Infections - virology ; Receptors, Antigen, T-Cell - genetics ; Retrospective Studies ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; T cell receptors ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; T-Lymphocytes - virology ; Tumor Virus Infections - diagnosis ; Tumor Virus Infections - genetics ; Tumor Virus Infections - virology ; Virus Activation</subject><ispartof>American journal of transplantation, 2013-11, Vol.13 (11), p.2842-2854</ispartof><rights>Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4511-2b2a34f57697f5eeeb0cbe9dc62e7f0e05fd2941d21cdbe85adb7fd8c4be1b203</citedby><cites>FETCH-LOGICAL-c4511-2b2a34f57697f5eeeb0cbe9dc62e7f0e05fd2941d21cdbe85adb7fd8c4be1b203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.12431$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27962065$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24020931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dziubianau, M.</creatorcontrib><creatorcontrib>Hecht, J.</creatorcontrib><creatorcontrib>Kuchenbecker, L.</creatorcontrib><creatorcontrib>Sattler, A.</creatorcontrib><creatorcontrib>Stervbo, U.</creatorcontrib><creatorcontrib>Rödelsperger, C.</creatorcontrib><creatorcontrib>Nickel, P.</creatorcontrib><creatorcontrib>Neumann, A. U.</creatorcontrib><creatorcontrib>Robinson, P. N.</creatorcontrib><creatorcontrib>Mundlos, S.</creatorcontrib><creatorcontrib>Volk, H.‐D.</creatorcontrib><creatorcontrib>Thiel, A.</creatorcontrib><creatorcontrib>Reinke, P.</creatorcontrib><creatorcontrib>Babel, N.</creatorcontrib><title>TCR Repertoire Analysis by Next Generation Sequencing Allows Complex Differential Diagnosis of T Cell–Related Pathology</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Clonotype analysis is essential for complete characterization of antigen‐specific T cells. Moreover, knowledge on clonal identity allows tracking of antigen‐specific T cells in whole blood and tissue infiltrates and can provide information on antigenic specificity. Here, we developed a next generation sequencing (NGS)‐based platform for the highly quantitative clonotype characterization of T cells and determined requirements for the unbiased characterization of the input material (DNA, RNA, ex vivo derived or cell culture expanded T cells). Thereafter we performed T cell receptor (TCR) repertoire analysis of various specimens in clinical settings including cytomegalovirus (CMV), polyomavirus BK (BKV) reactivation and acute cellular allograft rejection. Our results revealed dynamic nature of virus‐specific T cell clonotypes; CMV reactivation was linked to appearance of new highly abundant antigen‐specific clonalities. Moreover, analysis of clonotype overlap between BKV‐, alloantigen‐specific T cell–, kidney allograft‐ and urine‐derived lymphocytes provided hints for the differential diagnosis of allograft dysfunction and enabled appropriate therapy adjustment. We believe that the established approach will provide insights into the regulation of virus‐specific/anti‐tumor immunity and has high diagnostic potential in the clinical routine.
This study describes the development and characterization of T cell receptor repertoire analysis based on Next Generation Sequencing and its application for complex differential diagnosis of posttransplant kidney dysfunction.</description><subject>Acute cellular rejection</subject><subject>Biological and medical sciences</subject><subject>BK Virus - genetics</subject><subject>BKV</subject><subject>Blood</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - immunology</subject><subject>Cytomegalovirus - pathogenicity</subject><subject>Cytomegalovirus Infections - diagnosis</subject><subject>Cytomegalovirus Infections - genetics</subject><subject>Cytomegalovirus Infections - virology</subject><subject>Diagnosis, Differential</subject><subject>differential diagnosis</subject><subject>Graft Rejection - genetics</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunology</subject><subject>kidney transplantation</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Lymphocytes</subject><subject>Medical sciences</subject><subject>next generation sequencing</subject><subject>Pathology</subject><subject>polyoma</subject><subject>Polyomavirus Infections - diagnosis</subject><subject>Polyomavirus Infections - genetics</subject><subject>Polyomavirus Infections - virology</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Retrospective Studies</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - pathology</subject><subject>T-Lymphocytes - virology</subject><subject>Tumor Virus Infections - diagnosis</subject><subject>Tumor Virus Infections - genetics</subject><subject>Tumor Virus Infections - virology</subject><subject>Virus Activation</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0c1qGzEQB3BRUpqP9tAXKIJQSA9OJK208h7NNklbQltc97xI2pEjI68caU2yt7xD3rBPUjl2UygEqosk-DEzzB-ht5Sc0nzO1KI_pYwX9AU6oCUho5LyYu_pXYh9dJjSghAq2Zi9QvuME0aqgh6gYVZP8RRWEPvgIuBJp_yQXMJ6wF_hrseX0EFUvQsd_gE3a-iM6-Z44n24TbgOy5WHO_zRWQsRut4pnz9q3oVNjWDxDNfg_a_7hyl41UOLv6v-OvgwH16jl1b5BG929xH6eXE-qz-Nrr5dfq4nVyPDBaUjppkquBWyrKQVAKCJ0VC1pmQgLQEibMsqTltGTathLFSrpW3HhmugmpHiCJ1s665iyPOnvlm6ZPJQqoOwTg3lZW7EK_I_lEtKKipEpsf_0EVYx7y8RyXGTDJZZPVhq0wMKUWwzSq6pYpDQ0mzia7J0TWP0WX7bldxrZfQPsk_WWXwfgdUMsrbqHIW6a-TVclIuRntbOtunYfh-Y7N5Mts2_o3TdmwxQ</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Dziubianau, M.</creator><creator>Hecht, J.</creator><creator>Kuchenbecker, L.</creator><creator>Sattler, A.</creator><creator>Stervbo, U.</creator><creator>Rödelsperger, C.</creator><creator>Nickel, P.</creator><creator>Neumann, A. U.</creator><creator>Robinson, P. N.</creator><creator>Mundlos, S.</creator><creator>Volk, H.‐D.</creator><creator>Thiel, A.</creator><creator>Reinke, P.</creator><creator>Babel, N.</creator><general>Wiley</general><general>Elsevier Limited</general><scope>IQODW</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>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201311</creationdate><title>TCR Repertoire Analysis by Next Generation Sequencing Allows Complex Differential Diagnosis of T Cell–Related Pathology</title><author>Dziubianau, M. ; Hecht, J. ; Kuchenbecker, L. ; Sattler, A. ; Stervbo, U. ; Rödelsperger, C. ; Nickel, P. ; Neumann, A. U. ; Robinson, P. 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Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>T cell receptors</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - pathology</topic><topic>T-Lymphocytes - virology</topic><topic>Tumor Virus Infections - diagnosis</topic><topic>Tumor Virus Infections - genetics</topic><topic>Tumor Virus Infections - virology</topic><topic>Virus Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dziubianau, M.</creatorcontrib><creatorcontrib>Hecht, J.</creatorcontrib><creatorcontrib>Kuchenbecker, L.</creatorcontrib><creatorcontrib>Sattler, A.</creatorcontrib><creatorcontrib>Stervbo, U.</creatorcontrib><creatorcontrib>Rödelsperger, C.</creatorcontrib><creatorcontrib>Nickel, P.</creatorcontrib><creatorcontrib>Neumann, A. U.</creatorcontrib><creatorcontrib>Robinson, P. 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U.</au><au>Robinson, P. N.</au><au>Mundlos, S.</au><au>Volk, H.‐D.</au><au>Thiel, A.</au><au>Reinke, P.</au><au>Babel, N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TCR Repertoire Analysis by Next Generation Sequencing Allows Complex Differential Diagnosis of T Cell–Related Pathology</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2013-11</date><risdate>2013</risdate><volume>13</volume><issue>11</issue><spage>2842</spage><epage>2854</epage><pages>2842-2854</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>Clonotype analysis is essential for complete characterization of antigen‐specific T cells. Moreover, knowledge on clonal identity allows tracking of antigen‐specific T cells in whole blood and tissue infiltrates and can provide information on antigenic specificity. Here, we developed a next generation sequencing (NGS)‐based platform for the highly quantitative clonotype characterization of T cells and determined requirements for the unbiased characterization of the input material (DNA, RNA, ex vivo derived or cell culture expanded T cells). Thereafter we performed T cell receptor (TCR) repertoire analysis of various specimens in clinical settings including cytomegalovirus (CMV), polyomavirus BK (BKV) reactivation and acute cellular allograft rejection. Our results revealed dynamic nature of virus‐specific T cell clonotypes; CMV reactivation was linked to appearance of new highly abundant antigen‐specific clonalities. Moreover, analysis of clonotype overlap between BKV‐, alloantigen‐specific T cell–, kidney allograft‐ and urine‐derived lymphocytes provided hints for the differential diagnosis of allograft dysfunction and enabled appropriate therapy adjustment. We believe that the established approach will provide insights into the regulation of virus‐specific/anti‐tumor immunity and has high diagnostic potential in the clinical routine.
This study describes the development and characterization of T cell receptor repertoire analysis based on Next Generation Sequencing and its application for complex differential diagnosis of posttransplant kidney dysfunction.</abstract><cop>Hoboken, NJ</cop><pub>Wiley</pub><pmid>24020931</pmid><doi>10.1111/ajt.12431</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of transplantation, 2013-11, Vol.13 (11), p.2842-2854 |
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| language | eng |
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| subjects | Acute cellular rejection Biological and medical sciences BK Virus - genetics BKV Blood Cytomegalovirus Cytomegalovirus - immunology Cytomegalovirus - pathogenicity Cytomegalovirus Infections - diagnosis Cytomegalovirus Infections - genetics Cytomegalovirus Infections - virology Diagnosis, Differential differential diagnosis Graft Rejection - genetics High-Throughput Nucleotide Sequencing Humans Immunology kidney transplantation Kidney Transplantation - adverse effects Lymphocytes Medical sciences next generation sequencing Pathology polyoma Polyomavirus Infections - diagnosis Polyomavirus Infections - genetics Polyomavirus Infections - virology Receptors, Antigen, T-Cell - genetics Retrospective Studies Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system T cell receptors T-Lymphocytes - immunology T-Lymphocytes - pathology T-Lymphocytes - virology Tumor Virus Infections - diagnosis Tumor Virus Infections - genetics Tumor Virus Infections - virology Virus Activation |
| title | TCR Repertoire Analysis by Next Generation Sequencing Allows Complex Differential Diagnosis of T Cell–Related Pathology |
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