Cytotoxic T Cells to an Epitope in the Islet Autoantigen IA-2 Are Not Disease-Specific
Cytotoxic CD8 T lymphocytes (CTL) are effectors of pancreatic islet β-cell destruction in type 1 diabetes but, with the exception of a single report, CTL to islet antigen peptides have not been identified. We used autologous blood monocyte-derived dendritic cells to elicit HLA-A2-restricted CTL to a...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2001-06, Vol.99 (3), p.360-364 |
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| container_end_page | 364 |
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| container_title | Clinical immunology (Orlando, Fla.) |
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| creator | Takahashi, Kazuma Honeyman, Margo C. Harrison, Leonard C. |
| description | Cytotoxic CD8 T lymphocytes (CTL) are effectors of pancreatic islet β-cell destruction in type 1 diabetes but, with the exception of a single report, CTL to islet antigen peptides have not been identified. We used autologous blood monocyte-derived dendritic cells to elicit HLA-A2-restricted CTL to a peptide, MVWESGCTV (aa 797–805), that is contiguous with a dominant CD4 T-cell epitope in the islet antigen tyrosine phosphatase IA-2. IA-2 peptide-specific CTL activity measured as 51Cr release from autologous lymphoblasts was detected in 2/6 islet antibody-positive relatives at high risk for type 1 diabetes but also in 2/6 closely HLA-matched controls. All subjects had CTL activity to an HLA-A2-restricted Epstein–Barr virus peptide. CTL to the IA-2 self-peptide were therefore not disease-specific, consistent with other evidence that autoreactive T cells are present in healthy individuals. |
| doi_str_mv | 10.1006/clim.2001.5031 |
| format | Article |
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We used autologous blood monocyte-derived dendritic cells to elicit HLA-A2-restricted CTL to a peptide, MVWESGCTV (aa 797–805), that is contiguous with a dominant CD4 T-cell epitope in the islet antigen tyrosine phosphatase IA-2. IA-2 peptide-specific CTL activity measured as 51Cr release from autologous lymphoblasts was detected in 2/6 islet antibody-positive relatives at high risk for type 1 diabetes but also in 2/6 closely HLA-matched controls. All subjects had CTL activity to an HLA-A2-restricted Epstein–Barr virus peptide. CTL to the IA-2 self-peptide were therefore not disease-specific, consistent with other evidence that autoreactive T cells are present in healthy individuals.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1006/clim.2001.5031</identifier><identifier>PMID: 11358432</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Autoantibodies - immunology ; Biological and medical sciences ; CD8 antigen ; Child ; chromium ; cytotoxic ; dendritic cell ; Dendritic Cells - physiology ; Diabetes Mellitus, Type 1 - immunology ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Epitopes ; Epstein-Barr virus ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; General aspects ; histocompatibility antigen HLA ; HLA ; HLA-A2 Antigen - metabolism ; Humans ; IA-2 antigen ; Immunopathology ; Male ; Medical sciences ; Middle Aged ; T lymphocyte ; T-Lymphocytes, Cytotoxic - immunology ; type 1 diabetes ; tyrosine phosphatase IA-2</subject><ispartof>Clinical immunology (Orlando, Fla.), 2001-06, Vol.99 (3), p.360-364</ispartof><rights>2001 Academic Press</rights><rights>2001 INIST-CNRS</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-715ad28be82569a9f4c7ab5cf52a87cc5a26a2a43376d17546d86c729ada80863</citedby><cites>FETCH-LOGICAL-c400t-715ad28be82569a9f4c7ab5cf52a87cc5a26a2a43376d17546d86c729ada80863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/clim.2001.5031$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1145258$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11358432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takahashi, Kazuma</creatorcontrib><creatorcontrib>Honeyman, Margo C.</creatorcontrib><creatorcontrib>Harrison, Leonard C.</creatorcontrib><title>Cytotoxic T Cells to an Epitope in the Islet Autoantigen IA-2 Are Not Disease-Specific</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Cytotoxic CD8 T lymphocytes (CTL) are effectors of pancreatic islet β-cell destruction in type 1 diabetes but, with the exception of a single report, CTL to islet antigen peptides have not been identified. We used autologous blood monocyte-derived dendritic cells to elicit HLA-A2-restricted CTL to a peptide, MVWESGCTV (aa 797–805), that is contiguous with a dominant CD4 T-cell epitope in the islet antigen tyrosine phosphatase IA-2. IA-2 peptide-specific CTL activity measured as 51Cr release from autologous lymphoblasts was detected in 2/6 islet antibody-positive relatives at high risk for type 1 diabetes but also in 2/6 closely HLA-matched controls. All subjects had CTL activity to an HLA-A2-restricted Epstein–Barr virus peptide. CTL to the IA-2 self-peptide were therefore not disease-specific, consistent with other evidence that autoreactive T cells are present in healthy individuals.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Autoantibodies - immunology</subject><subject>Biological and medical sciences</subject><subject>CD8 antigen</subject><subject>Child</subject><subject>chromium</subject><subject>cytotoxic</subject><subject>dendritic cell</subject><subject>Dendritic Cells - physiology</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Epitopes</subject><subject>Epstein-Barr virus</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>General aspects</subject><subject>histocompatibility antigen HLA</subject><subject>HLA</subject><subject>HLA-A2 Antigen - metabolism</subject><subject>Humans</subject><subject>IA-2 antigen</subject><subject>Immunopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>T lymphocyte</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>type 1 diabetes</subject><subject>tyrosine phosphatase IA-2</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0D1v2zAQgGGiaNF8de0YcCi6ySUpkaJHw_kyELRDk6zE-XRKWMiiQtJB8-8rxwLSJchEDs8dyJexr1LMpBDmB3Z-M1NCyJkWpfzADqVWsqhFqT9Od2OkOWBHKf0RQmilzGd2IGWpbVWqQ3a3fM4hh78e-Q1fUtclngOHnp8PPoeBuO95fiC-Sh1lvtjmAH3299Tz1aJQfBGJ_wyZn_lEkKj4PRD61uMJ-9RCl-jLdB6z24vzm-VVcf3rcrVcXBdYCZGLWmpolF2TVdrMYd5WWMNaY6sV2BpRgzKgoCrL2jSy1pVprMFazaEBK6wpj9n3_d4hhsctpew2PuH4DegpbJOrR2SUmb8L5bhOmhc420OMIaVIrRui30B8dlK4XXK3S-52yd0u-ThwOm3erjfUvPKp8Qi-TQASQtdG6NGn_1yllbYjs3tGY68nT9El9NQjNT4SZtcE_9YT_gHH05of</recordid><startdate>20010601</startdate><enddate>20010601</enddate><creator>Takahashi, Kazuma</creator><creator>Honeyman, Margo C.</creator><creator>Harrison, Leonard C.</creator><general>Elsevier Inc</general><general>Elsevier</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20010601</creationdate><title>Cytotoxic T Cells to an Epitope in the Islet Autoantigen IA-2 Are Not Disease-Specific</title><author>Takahashi, Kazuma ; Honeyman, Margo C. ; Harrison, Leonard C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-715ad28be82569a9f4c7ab5cf52a87cc5a26a2a43376d17546d86c729ada80863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Autoantibodies - immunology</topic><topic>Biological and medical sciences</topic><topic>CD8 antigen</topic><topic>Child</topic><topic>chromium</topic><topic>cytotoxic</topic><topic>dendritic cell</topic><topic>Dendritic Cells - physiology</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Epitopes</topic><topic>Epstein-Barr virus</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>General aspects</topic><topic>histocompatibility antigen HLA</topic><topic>HLA</topic><topic>HLA-A2 Antigen - metabolism</topic><topic>Humans</topic><topic>IA-2 antigen</topic><topic>Immunopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>T lymphocyte</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>type 1 diabetes</topic><topic>tyrosine phosphatase IA-2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takahashi, Kazuma</creatorcontrib><creatorcontrib>Honeyman, Margo C.</creatorcontrib><creatorcontrib>Harrison, Leonard C.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takahashi, Kazuma</au><au>Honeyman, Margo C.</au><au>Harrison, Leonard C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxic T Cells to an Epitope in the Islet Autoantigen IA-2 Are Not Disease-Specific</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2001-06-01</date><risdate>2001</risdate><volume>99</volume><issue>3</issue><spage>360</spage><epage>364</epage><pages>360-364</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><coden>CLIIFY</coden><abstract>Cytotoxic CD8 T lymphocytes (CTL) are effectors of pancreatic islet β-cell destruction in type 1 diabetes but, with the exception of a single report, CTL to islet antigen peptides have not been identified. We used autologous blood monocyte-derived dendritic cells to elicit HLA-A2-restricted CTL to a peptide, MVWESGCTV (aa 797–805), that is contiguous with a dominant CD4 T-cell epitope in the islet antigen tyrosine phosphatase IA-2. IA-2 peptide-specific CTL activity measured as 51Cr release from autologous lymphoblasts was detected in 2/6 islet antibody-positive relatives at high risk for type 1 diabetes but also in 2/6 closely HLA-matched controls. All subjects had CTL activity to an HLA-A2-restricted Epstein–Barr virus peptide. CTL to the IA-2 self-peptide were therefore not disease-specific, consistent with other evidence that autoreactive T cells are present in healthy individuals.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>11358432</pmid><doi>10.1006/clim.2001.5031</doi><tpages>5</tpages></addata></record> |
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| subjects | Adolescent Adult Autoantibodies - immunology Biological and medical sciences CD8 antigen Child chromium cytotoxic dendritic cell Dendritic Cells - physiology Diabetes Mellitus, Type 1 - immunology Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Epitopes Epstein-Barr virus Etiopathogenesis. Screening. Investigations. Target tissue resistance Female General aspects histocompatibility antigen HLA HLA HLA-A2 Antigen - metabolism Humans IA-2 antigen Immunopathology Male Medical sciences Middle Aged T lymphocyte T-Lymphocytes, Cytotoxic - immunology type 1 diabetes tyrosine phosphatase IA-2 |
| title | Cytotoxic T Cells to an Epitope in the Islet Autoantigen IA-2 Are Not Disease-Specific |
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