A restricted clonal T-cell receptor αβ repertoire in Sézary syndrome is indicative of superantigenic stimulation
Summary Background Sézary syndrome (SS) is a cutaneous T‐cell lymphoma characterized by erythroderma, lymphadenopathy and malignant clonal T cells in the skin, lymph nodes and peripheral blood. A role for superantigens in the pathogenesis of SS has been postulated before. Objectives To investigate...
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| Veröffentlicht in: | British journal of dermatology (1951) 2011-07, Vol.165 (1), p.78-84 |
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| container_title | British journal of dermatology (1951) |
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| creator | van der Fits, L. Sandberg, Y. Darzentas, N. Zoutman, W.H. Tielemans, D. Wolvers-Tettero, I.L.M. Vermeer, M.H. Langerak, A.W. |
| description | Summary
Background Sézary syndrome (SS) is a cutaneous T‐cell lymphoma characterized by erythroderma, lymphadenopathy and malignant clonal T cells in the skin, lymph nodes and peripheral blood. A role for superantigens in the pathogenesis of SS has been postulated before.
Objectives To investigate a putative involvement of chronic (super‐)antigenic stimulation in driving T‐cell expansion in SS.
Methods Antigenic specificity of the T‐cell receptor (TCR) was assayed by molecular analysis of the TCRA (n = 11) and TCRB (n = 28) genes, followed by detailed in silico analysis.
Results Sequence analysis of clonally rearranged TCRB genes showed over‐representation of Vβ8, Vβ13, Vβ17, Vβ21 and Vβ22, and under‐representation of Vβ2 and Jβ1.1 when compared with healthy controls. No similarity was detected in amino acid motifs of the complementarity determining region 3 (CDR3). Analysis of TCRA rearrangements showed that there was no common Vα or Jα gene usage, and that TCRA CDR3 amino acid motifs were not highly similar.
Conclusions The lack of clear stereotypic TCRA and TCRB CDR3 amino acid motifs would argue against involvement of a single common antigen in the pathogenesis of SS. Nevertheless, the skewing of Vβ and Jβ gene usage does seem to point to a restricted TCR repertoire, possibly as a result of superantigenic selection prior to neoplastic transformation. |
| doi_str_mv | 10.1111/j.1365-2133.2011.10308.x |
| format | Article |
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Background Sézary syndrome (SS) is a cutaneous T‐cell lymphoma characterized by erythroderma, lymphadenopathy and malignant clonal T cells in the skin, lymph nodes and peripheral blood. A role for superantigens in the pathogenesis of SS has been postulated before.
Objectives To investigate a putative involvement of chronic (super‐)antigenic stimulation in driving T‐cell expansion in SS.
Methods Antigenic specificity of the T‐cell receptor (TCR) was assayed by molecular analysis of the TCRA (n = 11) and TCRB (n = 28) genes, followed by detailed in silico analysis.
Results Sequence analysis of clonally rearranged TCRB genes showed over‐representation of Vβ8, Vβ13, Vβ17, Vβ21 and Vβ22, and under‐representation of Vβ2 and Jβ1.1 when compared with healthy controls. No similarity was detected in amino acid motifs of the complementarity determining region 3 (CDR3). Analysis of TCRA rearrangements showed that there was no common Vα or Jα gene usage, and that TCRA CDR3 amino acid motifs were not highly similar.
Conclusions The lack of clear stereotypic TCRA and TCRB CDR3 amino acid motifs would argue against involvement of a single common antigen in the pathogenesis of SS. Nevertheless, the skewing of Vβ and Jβ gene usage does seem to point to a restricted TCR repertoire, possibly as a result of superantigenic selection prior to neoplastic transformation.</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/j.1365-2133.2011.10308.x</identifier><identifier>PMID: 21410672</identifier><identifier>CODEN: BJDEAZ</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Cells, Cultured ; Cohort Studies ; Dermatology ; Female ; Flow Cytometry ; Hematologic and hematopoietic diseases ; Humans ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Receptors, Antigen, T-Cell, alpha-beta - analysis ; Receptors, Antigen, T-Cell, alpha-beta - genetics ; Receptors, Antigen, T-Cell, alpha-beta - immunology ; Sequence Analysis, DNA ; Sezary Syndrome - immunology ; Skin Neoplasms - immunology ; Superantigens - immunology ; T-Lymphocytes - immunology</subject><ispartof>British journal of dermatology (1951), 2011-07, Vol.165 (1), p.78-84</ispartof><rights>2011 The Authors. BJD © 2011 British Association of Dermatologists 2011</rights><rights>2015 INIST-CNRS</rights><rights>2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3038-882545b79b3d93d17a79beebbe2f1f329e31f33cb8fa77e262fbce64863233b33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2133.2011.10308.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2133.2011.10308.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24339374$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21410672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Fits, L.</creatorcontrib><creatorcontrib>Sandberg, Y.</creatorcontrib><creatorcontrib>Darzentas, N.</creatorcontrib><creatorcontrib>Zoutman, W.H.</creatorcontrib><creatorcontrib>Tielemans, D.</creatorcontrib><creatorcontrib>Wolvers-Tettero, I.L.M.</creatorcontrib><creatorcontrib>Vermeer, M.H.</creatorcontrib><creatorcontrib>Langerak, A.W.</creatorcontrib><title>A restricted clonal T-cell receptor αβ repertoire in Sézary syndrome is indicative of superantigenic stimulation</title><title>British journal of dermatology (1951)</title><addtitle>Br J Dermatol</addtitle><description>Summary
Background Sézary syndrome (SS) is a cutaneous T‐cell lymphoma characterized by erythroderma, lymphadenopathy and malignant clonal T cells in the skin, lymph nodes and peripheral blood. A role for superantigens in the pathogenesis of SS has been postulated before.
Objectives To investigate a putative involvement of chronic (super‐)antigenic stimulation in driving T‐cell expansion in SS.
Methods Antigenic specificity of the T‐cell receptor (TCR) was assayed by molecular analysis of the TCRA (n = 11) and TCRB (n = 28) genes, followed by detailed in silico analysis.
Results Sequence analysis of clonally rearranged TCRB genes showed over‐representation of Vβ8, Vβ13, Vβ17, Vβ21 and Vβ22, and under‐representation of Vβ2 and Jβ1.1 when compared with healthy controls. No similarity was detected in amino acid motifs of the complementarity determining region 3 (CDR3). Analysis of TCRA rearrangements showed that there was no common Vα or Jα gene usage, and that TCRA CDR3 amino acid motifs were not highly similar.
Conclusions The lack of clear stereotypic TCRA and TCRB CDR3 amino acid motifs would argue against involvement of a single common antigen in the pathogenesis of SS. Nevertheless, the skewing of Vβ and Jβ gene usage does seem to point to a restricted TCR repertoire, possibly as a result of superantigenic selection prior to neoplastic transformation.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Cohort Studies</subject><subject>Dermatology</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - analysis</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - genetics</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - immunology</subject><subject>Sequence Analysis, DNA</subject><subject>Sezary Syndrome - immunology</subject><subject>Skin Neoplasms - immunology</subject><subject>Superantigens - immunology</subject><subject>T-Lymphocytes - immunology</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc1u1DAUha0K1A6FV0DeVKwSbN8kTjaVOi20wAgWFHVpOc4N8jQ_UzspM7wRS3gF9n0mnM508Oba93w60vEhhHIW83DeLmMOWRoJDhALxnnMGbA8Xh-Q2V54RmaMMRmxIoMj8sL7JWMcWMoOyZHgCWeZFDPiz6hDPzhrBqyoafpON_Q6Mtg0QTC4GnpHH34__AmvFbqhtw6p7ejXv79-arehftNVrm_Dzod1ZY0e7D3SvqZ-DLzuBvsdO2uoH2w7NkHtu5fkea0bj69285h8e__u-vwqWny5_HB-togMMMijPBdpkpayKKEqoOJShytiWaKoeQ2iQAgDTJnXWkoUmahLg1mSZyAASoBj8mbru3L93RhSqtb6KZnusB-9ymXCA8ySQL7ekWPZYqVWzrYhnXr6pwCc7ADtjW7qEMxY_59LAAqQk9HplvthG9zsdc7U1JtaqqkeNdWjpt7UY29qreYfLx6vwSDaGlg_4HpvoN2tyiTIVN18vlQLEFfsZv5JzeEfXGSdvw</recordid><startdate>201107</startdate><enddate>201107</enddate><creator>van der Fits, L.</creator><creator>Sandberg, Y.</creator><creator>Darzentas, N.</creator><creator>Zoutman, W.H.</creator><creator>Tielemans, D.</creator><creator>Wolvers-Tettero, I.L.M.</creator><creator>Vermeer, M.H.</creator><creator>Langerak, A.W.</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201107</creationdate><title>A restricted clonal T-cell receptor αβ repertoire in Sézary syndrome is indicative of superantigenic stimulation</title><author>van der Fits, L. ; Sandberg, Y. ; Darzentas, N. ; Zoutman, W.H. ; Tielemans, D. ; Wolvers-Tettero, I.L.M. ; Vermeer, M.H. ; Langerak, A.W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3038-882545b79b3d93d17a79beebbe2f1f329e31f33cb8fa77e262fbce64863233b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Cohort Studies</topic><topic>Dermatology</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - analysis</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - genetics</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - immunology</topic><topic>Sequence Analysis, DNA</topic><topic>Sezary Syndrome - immunology</topic><topic>Skin Neoplasms - immunology</topic><topic>Superantigens - immunology</topic><topic>T-Lymphocytes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Fits, L.</creatorcontrib><creatorcontrib>Sandberg, Y.</creatorcontrib><creatorcontrib>Darzentas, N.</creatorcontrib><creatorcontrib>Zoutman, W.H.</creatorcontrib><creatorcontrib>Tielemans, D.</creatorcontrib><creatorcontrib>Wolvers-Tettero, I.L.M.</creatorcontrib><creatorcontrib>Vermeer, M.H.</creatorcontrib><creatorcontrib>Langerak, A.W.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Fits, L.</au><au>Sandberg, Y.</au><au>Darzentas, N.</au><au>Zoutman, W.H.</au><au>Tielemans, D.</au><au>Wolvers-Tettero, I.L.M.</au><au>Vermeer, M.H.</au><au>Langerak, A.W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A restricted clonal T-cell receptor αβ repertoire in Sézary syndrome is indicative of superantigenic stimulation</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2011-07</date><risdate>2011</risdate><volume>165</volume><issue>1</issue><spage>78</spage><epage>84</epage><pages>78-84</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><coden>BJDEAZ</coden><abstract>Summary
Background Sézary syndrome (SS) is a cutaneous T‐cell lymphoma characterized by erythroderma, lymphadenopathy and malignant clonal T cells in the skin, lymph nodes and peripheral blood. A role for superantigens in the pathogenesis of SS has been postulated before.
Objectives To investigate a putative involvement of chronic (super‐)antigenic stimulation in driving T‐cell expansion in SS.
Methods Antigenic specificity of the T‐cell receptor (TCR) was assayed by molecular analysis of the TCRA (n = 11) and TCRB (n = 28) genes, followed by detailed in silico analysis.
Results Sequence analysis of clonally rearranged TCRB genes showed over‐representation of Vβ8, Vβ13, Vβ17, Vβ21 and Vβ22, and under‐representation of Vβ2 and Jβ1.1 when compared with healthy controls. No similarity was detected in amino acid motifs of the complementarity determining region 3 (CDR3). Analysis of TCRA rearrangements showed that there was no common Vα or Jα gene usage, and that TCRA CDR3 amino acid motifs were not highly similar.
Conclusions The lack of clear stereotypic TCRA and TCRB CDR3 amino acid motifs would argue against involvement of a single common antigen in the pathogenesis of SS. Nevertheless, the skewing of Vβ and Jβ gene usage does seem to point to a restricted TCR repertoire, possibly as a result of superantigenic selection prior to neoplastic transformation.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21410672</pmid><doi>10.1111/j.1365-2133.2011.10308.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Aged Biological and medical sciences Cells, Cultured Cohort Studies Dermatology Female Flow Cytometry Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Receptors, Antigen, T-Cell, alpha-beta - analysis Receptors, Antigen, T-Cell, alpha-beta - genetics Receptors, Antigen, T-Cell, alpha-beta - immunology Sequence Analysis, DNA Sezary Syndrome - immunology Skin Neoplasms - immunology Superantigens - immunology T-Lymphocytes - immunology |
| title | A restricted clonal T-cell receptor αβ repertoire in Sézary syndrome is indicative of superantigenic stimulation |
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