Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia
Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia
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DOI：
10.1007/s00726-010-0554-y
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发表时间：
2010-11-01
期刊：
影响因子：
3.5
通讯作者：
Sollid, Ludvig M.
中科院分区：
文献类型：
--
作者：
Stamnaes, Jorunn;Dorum, Siri;Sollid, Ludvig M.
转氨酶2（TG 2）是乳糜泻的主要自身抗原。TG2脱酰胺和交联谷蛋白肽的能力对于TG2特异性自身抗体的谷蛋白依赖性产生是必不可少的。在谷蛋白敏感性的主要肠外表现的患者中，自身抗体库可能不同。在疱疹样皮炎（DH）中，TG3似乎是靶自身抗原，而在谷蛋白共济失调（GA）中，存在与TG6反应的自身抗体。TG3和TG6在这些疾病中的功能作用尚未被描述。也不知道这些酶是否可以使用与病理学有关的谷蛋白肽作为底物。我们在这里报告，类似于TG2，TG3和TG6可以特异性脱酰胺谷蛋白T细胞表位。然而，发现酶的精细特异性不同。TG2可以通过异肽和硫酯键与谷蛋白形成共价复合物。我们发现TG3和TG6都能够通过硫酯键与谷蛋白肽复合，尽管效率低于TG2，而TG6而不是TG3能够形成异肽连接的复合物。我们的研究结果提供了可信的概念，即TG3和TG6参与谷蛋白诱导的DH和GA的自身免疫反应。
Transglutaminase 2 (TG2) is well characterized as the main autoantigen of celiac disease. The ability of TG2 to deamidate and crosslink gluten peptides is essential for the gluten-dependent production of TG2 specific autoantibodies. In patients with primarily extraintestinal manifestation of gluten sensitivity the repertoire of autoantibodies may be different. In dermatitis herpetiformis (DH), TG3 appears to be the target autoantigen whereas in gluten ataxia (GA) autoantibodies reactive with TG6 are present. A functional role for TG3 and TG6 in these diseases has yet to be described. It is also not known whether these enzymes can use gluten peptides implicated in the pathology as substrates. We here report that similar to TG2, TG3 and TG6 can specifically deamidate gluten T cell epitopes. However, the fine specificities of the enzymes were found to differ. TG2 can form covalent complexes with gluten by iso-peptide and thioester bonds. We found that both TG3 and TG6 were able to complex with gluten peptides through thioester linkage although less efficiently than TG2, whereas TG6 but not TG3 was able to form iso-peptide linked complexes. Our findings lend credence to the notion that TG3 and TG6 are involved in the gluten-induced autoimmune responses of DH and GA.