研究人员已经准确地找到了激发乳糜泻这种引起人们无法消化麸质蛋白的消化性疾病的免疫反应的分子原因。麸质存在于面包、谷物、意大利面食、曲奇饼、啤酒及许多其它内含小麦、大麦或黑麦的食品中。
这些发现可帮助人们创建诊断、预防和治疗乳糜泻的方法，特别是在那些具有异感遗传质的人中。 在罹患乳糜泻的个人中，进食含有麸质的食物会引起可损伤肠绒毛的免疫反应。绒毛是小肠内衬的毛法状突起，它们会从食物中攫取维生素、矿物质和其它的营养素。 在患病一段时间之后，由于不能够吸收合适量的营养素，从而造成这些乳糜泻病人维生素的缺乏，并会影响到其脑子、神经系统、骨头、肝脏和其它器官。 迄今为止，处理这种疾病的唯一方法是终身不碰含有麸质的食物。 即使如此，肠道的恢复也会因为存在的痕量污染麸质而受到损害。 例如，在那些采用了无麸质饮食的所有罹患乳糜泻的成年人中，大约有一半的人在5年之后仍然有肠道的损害。
在自从发现麸质是引起乳糜泻的环境因子之后的60年中，人们一直在寻找引起乳糜泻的一种毒性的麸质肽或几种肽。如今，Jason Tye-Din及其同事用图表显示了超过200个罹患乳糜泻的志愿者的免疫反应，这一数字比先前的研究数字要高出10倍。研究人员在那些进食了小麦、大麦或黑麦达3天时间以激活其对麸质的免疫反应的病人中开发出了一种简单的运算法则来对数千个肽（即组建蛋白质的分子）进行筛选。他们发现，一种从前被忽视的肽会引起患者的由小麦、大麦和黑麦所造成的共有的毒性。具有同样重要性的是，他们发现，仅对3种麸质肽具有特异性的被称作T细胞的免疫细胞与大多数的对麸质的免疫反应有关。这些发现支持某种长期存在但却未经证实的假说，即乳糜泻是由仅对少数主要的肽具有高度特异性的致病性T细胞所引起的。
推荐原文出处：
Sci Transl Med DOI: 10.1126/scitranslmed.3001012
Comprehensive, Quantitative Mapping of T Cell Epitopes in Gluten in Celiac Disease
Jason A. Tye-Din1,2,3,*, Jessica A. Stewart1,*, James A. Dromey1,*, Tim Beissbarth1,*?, David A. van Heel4, Arthur Tatham5, Kate Henderson6, Stuart I. Mannering1,?, Carmen Gianfrani7, Derek P. Jewell8, Adrian V. S. Hill9, James McCluskey10, Jamie Rossjohn6 and Robert P. Anderson1,3,§
1Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
3Department of Gastroenterology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia.
4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
5Cardiff School of Health Sciences, University of Wales Institute, Cardiff CF5 2YB, UK.
6Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
7Institute of Food Science, National Research Council, Via Roma 52, 83100 Avellino, Italy.
8Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
9Jenner Institute, University of Oxford, Oxford OX3 9DU, UK.
10Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4+ T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat α-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from ω-gliadin (wheat) and C-hordein (barley) but not α-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible.
