HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor
HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-...
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| Veröffentlicht in: | The Journal of experimental medicine 2004-12, Vol.200 (12), p.1547-1557 |
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| container_title | The Journal of experimental medicine |
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| creator | Dong, Tao Stewart-Jones, Guillaume Chen, Nan Easterbrook, Philippa Xu, Xiaoning Papagno, Laura Appay, Victor Weekes, Michael Conlon, Chris Spina, Celsa Little, Susan Screaton, Gavin van der Merwe, Anton Richman, Douglas D McMichael, Andrew J Jones, E Yvonne Rowland-Jones, Sarah L |
| description | HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome. |
| doi_str_mv | 10.1084/jem.20032044 |
| format | Article |
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In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>EISSN: 1892-1007</identifier><identifier>DOI: 10.1084/jem.20032044</identifier><identifier>PMID: 15596521</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Apoptosis - immunology ; Epitopes, T-Lymphocyte - immunology ; Female ; Gene Products, nef - immunology ; HIV Infections - immunology ; HIV Infections - pathology ; HIV-1 - immunology ; HIV-1 - physiology ; HLA-B8 Antigen - immunology ; Human immunodeficiency virus 1 ; Humans ; Male ; nef Gene Products, Human Immunodeficiency Virus ; Oligopeptides - immunology ; Prognosis ; Receptors, Antigen, T-Cell, alpha-beta - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Virus Replication - immunology</subject><ispartof>The Journal of experimental medicine, 2004-12, Vol.200 (12), p.1547-1557</ispartof><rights>Copyright © 2004, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-c9b5f3d4f84cb313feb1f721b237d78a9ce3217bf9fa9b2f07cde5df6a0cd1e73</citedby><cites>FETCH-LOGICAL-c413t-c9b5f3d4f84cb313feb1f721b237d78a9ce3217bf9fa9b2f07cde5df6a0cd1e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15596521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dong, Tao</creatorcontrib><creatorcontrib>Stewart-Jones, Guillaume</creatorcontrib><creatorcontrib>Chen, Nan</creatorcontrib><creatorcontrib>Easterbrook, Philippa</creatorcontrib><creatorcontrib>Xu, Xiaoning</creatorcontrib><creatorcontrib>Papagno, Laura</creatorcontrib><creatorcontrib>Appay, Victor</creatorcontrib><creatorcontrib>Weekes, Michael</creatorcontrib><creatorcontrib>Conlon, Chris</creatorcontrib><creatorcontrib>Spina, Celsa</creatorcontrib><creatorcontrib>Little, Susan</creatorcontrib><creatorcontrib>Screaton, Gavin</creatorcontrib><creatorcontrib>van der Merwe, Anton</creatorcontrib><creatorcontrib>Richman, Douglas D</creatorcontrib><creatorcontrib>McMichael, Andrew J</creatorcontrib><creatorcontrib>Jones, E Yvonne</creatorcontrib><creatorcontrib>Rowland-Jones, Sarah L</creatorcontrib><title>HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.</description><subject>Apoptosis - immunology</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Female</subject><subject>Gene Products, nef - immunology</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - pathology</subject><subject>HIV-1 - immunology</subject><subject>HIV-1 - physiology</subject><subject>HLA-B8 Antigen - immunology</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Male</subject><subject>nef Gene Products, Human Immunodeficiency Virus</subject><subject>Oligopeptides - immunology</subject><subject>Prognosis</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Virus Replication - immunology</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1892-1007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctLxDAQxoMouq7ePEtOnuyaSdKmvQgiPhYELz6OIU0na6Vt1qRd9L-34vo6eZqB-c3HfPMRcgBsBiyXJ8_YzjhjgjMpN8gEUsmSIhX5JpkwxnkCjKkdshvjM2MgZZptkx1I0yJLOUzI4_X8IYlLtLWrLbVvve_969jdUYtNE6kLvqWN7xZJj6GlcQireuVDpBEbtD01dOjqlwHXCzSgxWXvwx7ZcqaJuL-uU3J_eXF3fp3c3F7Nz89uEitB9IktytSJSrpc2lKAcFiCUxxKLlSlclNYFBxU6QpnipI7pmyFaeUyw2wFqMSUnH7qLoeyxcpi1wfT6GWoWxPetDe1_jvp6ie98CvNOYxfk6PA0Vog-NFH7HVbxw8rpkM_RJ0pyKXM1L8gKCUZiHwEjz9BG3yMAd33NcD0R2R6jEx_RTbih78d_MDrjMQ7IKeUTQ</recordid><startdate>20041220</startdate><enddate>20041220</enddate><creator>Dong, Tao</creator><creator>Stewart-Jones, Guillaume</creator><creator>Chen, Nan</creator><creator>Easterbrook, Philippa</creator><creator>Xu, Xiaoning</creator><creator>Papagno, Laura</creator><creator>Appay, Victor</creator><creator>Weekes, Michael</creator><creator>Conlon, Chris</creator><creator>Spina, Celsa</creator><creator>Little, Susan</creator><creator>Screaton, Gavin</creator><creator>van der Merwe, Anton</creator><creator>Richman, Douglas D</creator><creator>McMichael, Andrew J</creator><creator>Jones, E Yvonne</creator><creator>Rowland-Jones, Sarah L</creator><general>The Rockefeller 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>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20041220</creationdate><title>HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor</title><author>Dong, Tao ; Stewart-Jones, Guillaume ; Chen, Nan ; Easterbrook, Philippa ; Xu, Xiaoning ; Papagno, Laura ; Appay, Victor ; Weekes, Michael ; Conlon, Chris ; Spina, Celsa ; Little, Susan ; Screaton, Gavin ; van der Merwe, Anton ; Richman, Douglas D ; McMichael, Andrew J ; Jones, E Yvonne ; Rowland-Jones, Sarah L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-c9b5f3d4f84cb313feb1f721b237d78a9ce3217bf9fa9b2f07cde5df6a0cd1e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Apoptosis - immunology</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Female</topic><topic>Gene Products, nef - immunology</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - pathology</topic><topic>HIV-1 - immunology</topic><topic>HIV-1 - physiology</topic><topic>HLA-B8 Antigen - immunology</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Male</topic><topic>nef Gene Products, Human Immunodeficiency Virus</topic><topic>Oligopeptides - immunology</topic><topic>Prognosis</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - immunology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Virus Replication - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dong, Tao</creatorcontrib><creatorcontrib>Stewart-Jones, Guillaume</creatorcontrib><creatorcontrib>Chen, Nan</creatorcontrib><creatorcontrib>Easterbrook, Philippa</creatorcontrib><creatorcontrib>Xu, Xiaoning</creatorcontrib><creatorcontrib>Papagno, Laura</creatorcontrib><creatorcontrib>Appay, Victor</creatorcontrib><creatorcontrib>Weekes, Michael</creatorcontrib><creatorcontrib>Conlon, Chris</creatorcontrib><creatorcontrib>Spina, Celsa</creatorcontrib><creatorcontrib>Little, Susan</creatorcontrib><creatorcontrib>Screaton, Gavin</creatorcontrib><creatorcontrib>van der Merwe, Anton</creatorcontrib><creatorcontrib>Richman, Douglas D</creatorcontrib><creatorcontrib>McMichael, Andrew J</creatorcontrib><creatorcontrib>Jones, E Yvonne</creatorcontrib><creatorcontrib>Rowland-Jones, Sarah L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dong, Tao</au><au>Stewart-Jones, Guillaume</au><au>Chen, Nan</au><au>Easterbrook, Philippa</au><au>Xu, Xiaoning</au><au>Papagno, Laura</au><au>Appay, Victor</au><au>Weekes, Michael</au><au>Conlon, Chris</au><au>Spina, Celsa</au><au>Little, Susan</au><au>Screaton, Gavin</au><au>van der Merwe, Anton</au><au>Richman, Douglas D</au><au>McMichael, Andrew J</au><au>Jones, E Yvonne</au><au>Rowland-Jones, Sarah L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2004-12-20</date><risdate>2004</risdate><volume>200</volume><issue>12</issue><spage>1547</spage><epage>1557</epage><pages>1547-1557</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><eissn>1892-1007</eissn><abstract>HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>15596521</pmid><doi>10.1084/jem.20032044</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis - immunology Epitopes, T-Lymphocyte - immunology Female Gene Products, nef - immunology HIV Infections - immunology HIV Infections - pathology HIV-1 - immunology HIV-1 - physiology HLA-B8 Antigen - immunology Human immunodeficiency virus 1 Humans Male nef Gene Products, Human Immunodeficiency Virus Oligopeptides - immunology Prognosis Receptors, Antigen, T-Cell, alpha-beta - immunology T-Lymphocytes, Cytotoxic - immunology Virus Replication - immunology |
| title | HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor |
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