Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis.
Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis.
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自身免疫性肝炎可溶性肝抗原/肝胰自身抗原中CD4 T细胞表位的鉴定
DOI：
10.1053/j.gastro.2008.07.029
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发表时间：
2008
期刊：
影响因子：
29.4
通讯作者：
Rehermann B
中科院分区：
文献类型：
--
作者：
Weiler-Normann C;Thimme R;Ahlenstiel G;Shin EC;Herkel J;David CS;Lohse AW;Rehermann B
背景与目的自身免疫性肝炎（Autoimmune hepatitis，AIH）是一种与自身抗体和肝脏浸润淋巴细胞相关的慢性炎症性肝病。虽然自身抗体常规检测诊断和分类AIH，肝脏浸润淋巴细胞被认为是疾病发病机制的主要因素。本研究的目的是鉴定和鉴定人AIH特异性可溶性肝抗原/肝胰抗原（SLA/LP）中受疾病易感基因HLA-DRB 1 * 0301限制的、CD 4 +T细胞靶向的自身抗原肽。抗体和T细胞反应进行了分析与SLA/LP重叠肽在酶免疫分析，增殖，酶联免疫斑点（ELISpot）测定。最小的最佳T细胞表位进行了鉴定，其特征在于与克隆的T细胞杂交瘤，并确认在四聚体和ELISpot测定与AIH患者的外周血单核cells。T细胞靶向SLA/LP内的几种肽，其中2种是DR 3限制性的，一种与人自身抗体识别的序列重叠。最小的最佳表位作图，DRB 1 *0301/表位四聚体的产生，并在AIH患者的HLA-DRB 1 *0301限制性自身抗原特异性T细胞的频率和功能进行了分析与四聚体和干扰素-γ ELISpot assays.CONCLUSIONSThis研究确定T细胞表位SLA/LP，疾病易感基因DRB 1 *0301限制性和接近人类自身抗体表位。这些结果和产生的试剂现在提供了在临床研究中直接监测AIH患者中自身反应性T细胞的机会。
BACKGROUND & AIMSAutoimmune 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.METHODSHLA-DRB1*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.RESULTSAll 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, DRB1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoantigen-specific T cells in AIH patients were analyzed with tetramer and interferon-γ ELISpot assays.CONCLUSIONSThis 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.
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DOI：
10.1172/jci18509
发表时间：
2003-09
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
C. Day;Nilufer P. Seth;M. Lucas;H. Appel;L. Gauthier;G. Lauer;G. Robbins;Z. Szczepiorkowski;D. Casson;R. Chung;Shannon Bell;G. Harcourt;B. Walker;P. Klenerman;K. Wucherpfennig
通讯作者：
C. Day;Nilufer P. Seth;M. Lucas;H. Appel;L. Gauthier;G. Lauer;G. Robbins;Z. Szczepiorkowski;D. Casson;R. Chung;Shannon Bell;G. Harcourt;B. Walker;P. Klenerman;K. Wucherpfennig
自身免疫性肝炎——诊断方法。
DOI：
--
发表时间：
2006
期刊：
MedGenMed : Medscape general medicine
影响因子：
--
作者：
A. Czaja
通讯作者：
A. Czaja
影响因子：
3.7
作者：
Hoehn, H.;Kortsik, C.;Maeurer, M.
通讯作者：
Maeurer, M.
影响因子：
13.5
作者：
Yamauchi, K;Yamaguchi, N;Shiratori, K
通讯作者：
Shiratori, K
影响因子：
7.7
作者：
Reijonen, H;Mallone, R;Nepom, GT
通讯作者：
Nepom, GT