Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients.
Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients.
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DOI：
10.1084/jem.178.1.187
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发表时间：
1993-07-01
期刊：
影响因子：
--
通讯作者：
Sollid LM
中科院分区：
文献类型：
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作者：
Lundin KE;Scott H;Hansen T;Paulsen G;Halstensen TS;Fausa O;Thorsby E;Sollid LM
乳糜泻（CD）很可能是一种免疫性疾病，在易感个体中通过摄入小麦醇溶蛋白和来自其他谷物的相关蛋白而诱发。该疾病显示出主要与顺式或反式编码的HLA-DQ（α 1*0501，β 1*0201）（DQ 2）异二聚体的强人类HLA关联。因此，由DQ异源二聚体呈递的麦胶蛋白的T细胞识别在CD中可能具有免疫病理重要性。因此，我们在体外用麸质（含有麦胶蛋白和其他小麦蛋白）挑战来自成年CD患者的无麸质饮食的小肠活检，并分离活化的CD 25 + T细胞。建立了多克隆T细胞系和一组识别谷蛋白的T细胞克隆。他们识别出谷蛋白中的麦醇溶蛋白部分，但不识别其他谷物中的蛋白质。用抗HLA抗体进行的抑制研究证明了HLA-DQ分子的主要抗原呈递。主要抗原呈递分子被确定为CD相关DQ（α 1*0501，β 1*0201）异二聚体。谷蛋白反应性T细胞克隆是CD 4+、CD 8-，并且携带T细胞受体（TCR）V α和V β链的不同组合。研究结果表明，在CD中，HLA-DQ（α 1*0501，β 1*0201）优先粘膜呈递谷蛋白衍生肽，这可能解释HLA相关性。
Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA- DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen- presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association.