The T-Cell-Receptor Repertoire in the Synovial Fluid of a Patient with Rheumatoid Arthritis is Polyclonal
We have analyzed the T-cell-receptor repertoire expressed in the synovial fluid of a patient with rheumatoid arthritis by using an inverse polymerase chain reaction. Total RNA was isolated from Ficoll-purified mononuclear cells and converted into circularized double-stranded cDNA. Specific amplifica...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-10, Vol.88 (19), p.8534-8538 |
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creator | Uematsu, Yasushi Wege, Helmut Straus, Alexander Ott, Michael Bannwarth, Willi Lanchbury, Jerry Panayi, Gabriel Steinmetz, Michael |
description | We have analyzed the T-cell-receptor repertoire expressed in the synovial fluid of a patient with rheumatoid arthritis by using an inverse polymerase chain reaction. Total RNA was isolated from Ficoll-purified mononuclear cells and converted into circularized double-stranded cDNA. Specific amplification of α- and β-chain variable regions (Vα and Vβ) was achieved with inverted α- and β-chain constant region (Cα and Cβ) primer pairs, and the amplification products were cloned into phage vectors. A total of 78 α and 76 β clones were sequenced, and 67 and 72 productively rearranged α and β genes were identified, respectively. Thirty-one Vα, 33 α-chain joining region (Jα), 29 Vβ, and 12 β-chain joining region (Jβ) gene segments were found in the productively rearranged clones, indicating that the T-cell repertoire expressed in the synovial fluid of this RA patient is highly heterogenous and polyclonal. Comparison of peripheral blood and synovial fluid repertoires showed that the most abundant Vβ sequences, Vβ2.1 and Vβ3.1, were enriched in the inflamed joint by a factor of 2 to 3. It is possible that T cells expressing these Vβ gene segments, which recognize bacterial superantigens, play a role in the disease. |
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Total RNA was isolated from Ficoll-purified mononuclear cells and converted into circularized double-stranded cDNA. Specific amplification of α- and β-chain variable regions (Vα and Vβ) was achieved with inverted α- and β-chain constant region (Cα and Cβ) primer pairs, and the amplification products were cloned into phage vectors. A total of 78 α and 76 β clones were sequenced, and 67 and 72 productively rearranged α and β genes were identified, respectively. Thirty-one Vα, 33 α-chain joining region (Jα), 29 Vβ, and 12 β-chain joining region (Jβ) gene segments were found in the productively rearranged clones, indicating that the T-cell repertoire expressed in the synovial fluid of this RA patient is highly heterogenous and polyclonal. Comparison of peripheral blood and synovial fluid repertoires showed that the most abundant Vβ sequences, Vβ2.1 and Vβ3.1, were enriched in the inflamed joint by a factor of 2 to 3. It is possible that T cells expressing these Vβ gene segments, which recognize bacterial superantigens, play a role in the disease.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.19.8534</identifier><identifier>PMID: 1656449</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Arthritis, Rheumatoid - immunology ; Arthritis, Rheumatoid - pathology ; Autoimmune diseases ; Base Sequence ; Biological and medical sciences ; Blood ; Clone Cells ; Complementary DNA ; Diseases of the osteoarticular system ; DNA ; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; genes ; Humans ; Inflammatory joint diseases ; Joints ; Medical sciences ; Molecular Sequence Data ; Oligonucleotides - chemistry ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell, alpha-beta - genetics ; rheumatoid arthritis ; RNA ; Synovial fluid ; Synovial Membrane - immunology ; T cell antigen receptors ; T lymphocytes ; T-Lymphocytes - pathology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-10, Vol.88 (19), p.8534-8538</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-db6711acba71dd02fa57b5764574170bc9b0b6dae4e1c1d2496ee103936e5d833</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/19.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2357974$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2357974$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5011177$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1656449$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uematsu, Yasushi</creatorcontrib><creatorcontrib>Wege, Helmut</creatorcontrib><creatorcontrib>Straus, Alexander</creatorcontrib><creatorcontrib>Ott, Michael</creatorcontrib><creatorcontrib>Bannwarth, Willi</creatorcontrib><creatorcontrib>Lanchbury, Jerry</creatorcontrib><creatorcontrib>Panayi, Gabriel</creatorcontrib><creatorcontrib>Steinmetz, Michael</creatorcontrib><title>The T-Cell-Receptor Repertoire in the Synovial Fluid of a Patient with Rheumatoid Arthritis is Polyclonal</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We have analyzed the T-cell-receptor repertoire expressed in the synovial fluid of a patient with rheumatoid arthritis by using an inverse polymerase chain reaction. Total RNA was isolated from Ficoll-purified mononuclear cells and converted into circularized double-stranded cDNA. Specific amplification of α- and β-chain variable regions (Vα and Vβ) was achieved with inverted α- and β-chain constant region (Cα and Cβ) primer pairs, and the amplification products were cloned into phage vectors. A total of 78 α and 76 β clones were sequenced, and 67 and 72 productively rearranged α and β genes were identified, respectively. Thirty-one Vα, 33 α-chain joining region (Jα), 29 Vβ, and 12 β-chain joining region (Jβ) gene segments were found in the productively rearranged clones, indicating that the T-cell repertoire expressed in the synovial fluid of this RA patient is highly heterogenous and polyclonal. Comparison of peripheral blood and synovial fluid repertoires showed that the most abundant Vβ sequences, Vβ2.1 and Vβ3.1, were enriched in the inflamed joint by a factor of 2 to 3. It is possible that T cells expressing these Vβ gene segments, which recognize bacterial superantigens, play a role in the disease.</description><subject>Amino Acid Sequence</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Autoimmune diseases</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Clone Cells</subject><subject>Complementary DNA</subject><subject>Diseases of the osteoarticular system</subject><subject>DNA</subject><subject>Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor</subject><subject>Gene Rearrangement, beta-Chain T-Cell Antigen Receptor</subject><subject>genes</subject><subject>Humans</subject><subject>Inflammatory joint diseases</subject><subject>Joints</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotides - chemistry</subject><subject>Polymerase Chain Reaction</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - genetics</subject><subject>rheumatoid arthritis</subject><subject>RNA</subject><subject>Synovial fluid</subject><subject>Synovial Membrane - immunology</subject><subject>T cell antigen receptors</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - pathology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks2P1CAYxonRrOPq2YsaDkZPneUtUNrEy2biqskmbsbxTCillg1TRqCr899LM-PoXjQh4fD8nveDB4SeA1kCEfRiN6q4rOslNMuaU_YALYA0UFSsIQ_RgpBSFDUr2WP0JMZbQkjDa3KGzqDiFWPNAtnNYPCmWBnnirXRZpd8wGuzMyF5Gwy2I06Z-LIf_Z1VDl-5yXbY91jhG5WsGRP-YdOA14OZtip7OnwZ0hBsshHnc-PdXjs_KvcUPeqVi-bZ8T5HX6_eb1Yfi-vPHz6tLq8LzcsyFV1bCQClWyWg60jZKy5aLirGBQNBWt20pK06ZZgBDV3JmsoYILShleFdTek5eneou5varel0HjEoJ3fBblXYS6-svK-MdpDf_J3kJWez_c3RHvz3ycQktzbq_DxqNH6KUpTAasjt_gdCRSirKM_gxQHUwccYTH-aBYicQ5RziLKuJTRyDjE7Xv69wh_-kFrWXx91FbVyfVCjtvGEcQIAQmTs1RGb6_9W7_V5-09A9pNzyfxMmXxxIG9j_iAntKRcNILRX501yDE</recordid><startdate>19911001</startdate><enddate>19911001</enddate><creator>Uematsu, Yasushi</creator><creator>Wege, Helmut</creator><creator>Straus, Alexander</creator><creator>Ott, Michael</creator><creator>Bannwarth, Willi</creator><creator>Lanchbury, Jerry</creator><creator>Panayi, Gabriel</creator><creator>Steinmetz, Michael</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</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>7T3</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19911001</creationdate><title>The T-Cell-Receptor Repertoire in the Synovial Fluid of a Patient with Rheumatoid Arthritis is Polyclonal</title><author>Uematsu, Yasushi ; Wege, Helmut ; Straus, Alexander ; Ott, Michael ; Bannwarth, Willi ; Lanchbury, Jerry ; Panayi, Gabriel ; Steinmetz, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-db6711acba71dd02fa57b5764574170bc9b0b6dae4e1c1d2496ee103936e5d833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Amino Acid Sequence</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Autoimmune diseases</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Clone Cells</topic><topic>Complementary DNA</topic><topic>Diseases of the osteoarticular system</topic><topic>DNA</topic><topic>Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor</topic><topic>Gene Rearrangement, beta-Chain T-Cell Antigen Receptor</topic><topic>genes</topic><topic>Humans</topic><topic>Inflammatory joint diseases</topic><topic>Joints</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Oligonucleotides - chemistry</topic><topic>Polymerase Chain Reaction</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - genetics</topic><topic>rheumatoid arthritis</topic><topic>RNA</topic><topic>Synovial fluid</topic><topic>Synovial Membrane - immunology</topic><topic>T cell antigen receptors</topic><topic>T lymphocytes</topic><topic>T-Lymphocytes - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uematsu, Yasushi</creatorcontrib><creatorcontrib>Wege, Helmut</creatorcontrib><creatorcontrib>Straus, Alexander</creatorcontrib><creatorcontrib>Ott, Michael</creatorcontrib><creatorcontrib>Bannwarth, Willi</creatorcontrib><creatorcontrib>Lanchbury, Jerry</creatorcontrib><creatorcontrib>Panayi, Gabriel</creatorcontrib><creatorcontrib>Steinmetz, Michael</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Human Genome Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uematsu, Yasushi</au><au>Wege, Helmut</au><au>Straus, Alexander</au><au>Ott, Michael</au><au>Bannwarth, Willi</au><au>Lanchbury, Jerry</au><au>Panayi, Gabriel</au><au>Steinmetz, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The T-Cell-Receptor Repertoire in the Synovial Fluid of a Patient with Rheumatoid Arthritis is Polyclonal</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-10-01</date><risdate>1991</risdate><volume>88</volume><issue>19</issue><spage>8534</spage><epage>8538</epage><pages>8534-8538</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>We have analyzed the T-cell-receptor repertoire expressed in the synovial fluid of a patient with rheumatoid arthritis by using an inverse polymerase chain reaction. Total RNA was isolated from Ficoll-purified mononuclear cells and converted into circularized double-stranded cDNA. Specific amplification of α- and β-chain variable regions (Vα and Vβ) was achieved with inverted α- and β-chain constant region (Cα and Cβ) primer pairs, and the amplification products were cloned into phage vectors. A total of 78 α and 76 β clones were sequenced, and 67 and 72 productively rearranged α and β genes were identified, respectively. Thirty-one Vα, 33 α-chain joining region (Jα), 29 Vβ, and 12 β-chain joining region (Jβ) gene segments were found in the productively rearranged clones, indicating that the T-cell repertoire expressed in the synovial fluid of this RA patient is highly heterogenous and polyclonal. Comparison of peripheral blood and synovial fluid repertoires showed that the most abundant Vβ sequences, Vβ2.1 and Vβ3.1, were enriched in the inflamed joint by a factor of 2 to 3. It is possible that T cells expressing these Vβ gene segments, which recognize bacterial superantigens, play a role in the disease.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1656449</pmid><doi>10.1073/pnas.88.19.8534</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - pathology Autoimmune diseases Base Sequence Biological and medical sciences Blood Clone Cells Complementary DNA Diseases of the osteoarticular system DNA Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor Gene Rearrangement, beta-Chain T-Cell Antigen Receptor genes Humans Inflammatory joint diseases Joints Medical sciences Molecular Sequence Data Oligonucleotides - chemistry Polymerase Chain Reaction Receptors, Antigen, T-Cell, alpha-beta - genetics rheumatoid arthritis RNA Synovial fluid Synovial Membrane - immunology T cell antigen receptors T lymphocytes T-Lymphocytes - pathology |
title | The T-Cell-Receptor Repertoire in the Synovial Fluid of a Patient with Rheumatoid Arthritis is Polyclonal |
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