Skovbjerg H, Anthonsen D, Knudsen E, Sjöström H
Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
Dig Dis Sci. 2008 Nov;53(11):2917-24. doi: 10.1007/s10620-008-0450-4. Epub 2008 Aug 5.
Activation of small intestinal gluten-reactive CD4(+) T-cells is a critical event in celiac disease. Deamidation of specific glutamine residues by tissue transglutaminase enhances the binding of T-cell activating gliadin epitopes to DQ2, increasing T-cell recognition. Our purpose was to investigate whether deamidated gliadin epitopes can be generated in the small intestinal mucosa by tissue transglutaminase and to characterize the location of the process. Intestinal explants from pig intestine and frozen biopsy slices from human and rat intestine were incubated with alpha-gliadin peptides containing the immunodominant motif. Monoclonal antibodies specifically recognizing the non-deamidated and/or the deamidated epitope were used for immunofluorescence studies. We conclude that endogenous tissue transglutaminase can mediate extracellular deamidation of gliadin peptides in the lamina propria. Gliadin peptides with more than one recognition site can be simultaneously cross-linked and deamidated extracellularly in the lamina propria, and might be of importance for the antibody response seen in untreated celiac disease patients.
小肠中对麸质产生反应的CD4(+) T细胞的激活是乳糜泻中的一个关键事件。组织转谷氨酰胺酶使特定谷氨酰胺残基脱酰胺，增强了T细胞激活麦醇溶蛋白表位与DQ2的结合，增加了T细胞的识别。我们的目的是研究组织转谷氨酰胺酶是否能在小肠黏膜中产生脱酰胺的麦醇溶蛋白表位，并确定该过程的发生位置。将猪小肠的肠外植体以及人和大鼠小肠的冷冻活检切片与含有免疫显性基序的α-麦醇溶蛋白肽一起孵育。使用特异性识别未脱酰胺和/或脱酰胺表位的单克隆抗体进行免疫荧光研究。我们得出结论，内源性组织转谷氨酰胺酶可介导固有层中麦醇溶蛋白肽的细胞外脱酰胺。具有多个识别位点的麦醇溶蛋白肽可在固有层中同时进行细胞外交联和脱酰胺，这可能对未经治疗的乳糜泻患者中出现的抗体反应具有重要意义。
