DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mix, Heiko | ko |
dc.contributor.author | Weiler-Normann, Christina | ko |
dc.contributor.author | Thimme, Robert | ko |
dc.contributor.author | Ahlenstiel, Golo | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Herkel, Johannes | ko |
dc.contributor.author | David, Chella S. | ko |
dc.contributor.author | Lohse, Ansgar W. | ko |
dc.contributor.author | Rehermann, Barbara | ko |
dc.date.accessioned | 2009-11-30T08:38:27Z | - |
dc.date.available | 2009-11-30T08:38:27Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2008-12 | - |
dc.identifier.citation | GASTROENTEROLOGY, v.135, no.6, pp.2107 - 2118 | - |
dc.identifier.issn | 0016-5085 | - |
dc.identifier.uri | http://hdl.handle.net/10203/13709 | - |
dc.description | H.M. was supported by grant MI 677/1-1 and G.A. was supported by grant AH 173/1-1 from the Deutsche Forschungsgemeinschaft (Bonn, Germany); and J.H. and A.W.L. were supported by grant SFB 548 from the Deutsche Forschungsgemeinschaft. | en |
dc.description.abstract | Background & Aims: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with autoantibodies and liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoantigenic peptides within human AIH-specific soluble liver antigen/liver pancreas antigen (SLA/LP) that are targeted by CD4(+) T cells and restricted by the disease susceptibility gene HLA-DRB1*0301. Methods: HLADR-BI*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA/LP-overlapping peptides in enzyme immunoassay, proliferation, and enzyme-linked immunospot (ELISpot) assays. Minimal optimal T-cell epitopes were identified, characterized with cloned T-cell hybridomas, and confirmed in tetramer and ELISpot assays with AIH patients' peripheral blood mononuclear cells. Results: All mice developed SLA/LP-specific IgG1/IgG2a antibodies against the same SLA/LP peptides as human beings. T cells targeted several peptides within SLA/LP, 2 of which were DR3-restricted and one overlapped the sequence recognized by human autoantibodies. Minimal optimal epitopes were mapped, DR-B1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoandgen-specific T cells in AIH patients were analyzed with tetramer and interferon-gamma ELISpot assays. Conclusions: This study identified T-cell epitopes within SLA/LP, restricted by the disease susceptibility gene DRB1*0301 and in close proximity to the human autoantibody epitope. These results and the generated reagents now provide the opportunity to directly monitor autoreactive T cells in AIH patients in clinical studies. | - |
dc.description.sponsorship | This study was supported by the intramural research program of the National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health. | en |
dc.language | English | - |
dc.language.iso | en_US | en |
dc.publisher | W B SAUNDERS CO-ELSEVIER INC | - |
dc.subject | CLASS-II TETRAMERS | - |
dc.subject | CHRONIC ACTIVE HEPATITIS | - |
dc.subject | C VIRUS-INFECTION | - |
dc.subject | EX-VIVO ANALYSIS | - |
dc.subject | PERIPHERAL-BLOOD | - |
dc.subject | TRANSGENIC MICE | - |
dc.subject | AUTOANTIBODIES | - |
dc.subject | RESPONSES | - |
dc.subject | MODEL | - |
dc.subject | SUSCEPTIBILITY | - |
dc.title | Identification of CD4 T-Cell Epitopes in Soluble Liver Antigen/Liver Pancreas Autoantigen in Autoimmune Hepatitis | - |
dc.type | Article | - |
dc.identifier.wosid | 000261762200072 | - |
dc.identifier.scopusid | 2-s2.0-57349163208 | - |
dc.type.rims | ART | - |
dc.citation.volume | 135 | - |
dc.citation.issue | 6 | - |
dc.citation.beginningpage | 2107 | - |
dc.citation.endingpage | 2118 | - |
dc.citation.publicationname | GASTROENTEROLOGY | - |
dc.identifier.doi | 10.1053/j.gastro.2008.07.029 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Mix, Heiko | - |
dc.contributor.nonIdAuthor | Weiler-Normann, Christina | - |
dc.contributor.nonIdAuthor | Thimme, Robert | - |
dc.contributor.nonIdAuthor | Ahlenstiel, Golo | - |
dc.contributor.nonIdAuthor | Herkel, Johannes | - |
dc.contributor.nonIdAuthor | David, Chella S. | - |
dc.contributor.nonIdAuthor | Lohse, Ansgar W. | - |
dc.contributor.nonIdAuthor | Rehermann, Barbara | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | CLASS-II TETRAMERS | - |
dc.subject.keywordPlus | CHRONIC ACTIVE HEPATITIS | - |
dc.subject.keywordPlus | C VIRUS-INFECTION | - |
dc.subject.keywordPlus | EX-VIVO ANALYSIS | - |
dc.subject.keywordPlus | PERIPHERAL-BLOOD | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | AUTOANTIBODIES | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordPlus | SUSCEPTIBILITY | - |
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