Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes.
Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes.
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DOI：
10.1186/1471-2164-7-1
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发表时间：
2006-01-10
期刊：
影响因子：
4.4
通讯作者：
Smulders MJ
中科院分区：
文献类型：
--
作者：
van Herpen TW;Goryunova SV;van der Schoot J;Mitreva M;Salentijn E;Vorst O;Schenk MF;van Veelen PA;Koning F;van Soest LJ;Vosman B;Bosch D;Hamer RJ;Gilissen LJ;Smulders MJ
面包小麦（Triticum aestivum）是重要的主粮。然而，小麦麸质蛋白会导致 0.5% 至 1% 的普通人群患乳糜泻 (CD)。在这些蛋白质中，α-麦醇溶蛋白含有多种与疾病相关的肽。我们从几个二倍体小麦物种中获得了 230 个不同的 α-麦醇溶蛋白基因序列，代表了六倍体面包小麦的祖先 A、B 和 D 基因组。这些序列中的绝大多数（87%）包含内部终止密码子。所有 α-麦醇溶蛋白序列都可以根据序列相似性、多聚谷氨酰胺重复的平均长度以及四种肽存在的差异（通过与 HLA-DQ2/8 结合而被鉴定为 CD 患者中的 T 细胞刺激表位）的差异，根据起源基因组来区分。根据序列相似性，来自六倍体小麦公共数据库的 α-麦醇溶蛋白可以直接分配到染色体 6A、6B 或 6D。单球菌（A 基因组）序列以及面包小麦 6A 号染色体的序列几乎总是包含表位 glia-α9 和 glia-α20，但从未包含完整表位 glia-α 和 glia-α2。来自 T. speltoides 的许多序列以及来自面包小麦 6B 染色体的许多序列不包含筛选的四个 T 细胞表位中的任何一个。节节小麦（D 基因组）的序列以及面包小麦 6D 染色体的序列被发现在每个基因的可变组合中包含所有这些 T 细胞表位。表位组成的差异主要是由点突变造成的。这些取代似乎是基因组特异性的。我们的分析表明，来自面包小麦三个基因组的 α-麦醇溶蛋白序列形成不同的组。四个已知的 T 细胞刺激表位在序列中非随机分布，表明三个基因组对表位内容的贡献不同。对麦醇溶蛋白和麦谷蛋白中所有已知表位的系统分析将有助于更好地了解小麦品种之间的毒性差异。基于这种认识，可以设计育种策略来产生毒性较低的小麦品种，至少部分克罗恩病患者群体可以耐受。
Bread wheat (Triticum aestivum) is an important staple food. However, wheat gluten proteins cause celiac disease (CD) in 0.5 to 1% of the general population. Among these proteins, the α-gliadins contain several peptides that are associated to the disease. We obtained 230 distinct α-gliadin gene sequences from severaldiploid wheat species representing the ancestral A, B, and D genomes of the hexaploid bread wheat. The large majority of these sequences (87%) contained an internal stop codon. All α-gliadin sequences could be distinguished according to the genome of origin on the basis of sequence similarity, of the average length of the polyglutamine repeats, and of the differences in the presence of four peptides that have been identified as T cell stimulatory epitopes in CD patients through binding to HLA-DQ2/8. By sequence similarity, α-gliadins from the public database of hexaploid T. aestivum could be assigned directly to chromosome 6A, 6B, or 6D. T. monococcum (A genome) sequences, as well as those from chromosome 6A of bread wheat, almost invariably contained epitope glia-α9 and glia-α20, but never the intact epitopes glia-α and glia-α2. A number of sequences from T. speltoides, as well as a number of sequences fromchromosome 6B of bread wheat, did not contain any of the four T cell epitopes screened for. The sequences from T. tauschii (D genome), as well as those from chromosome 6D of bread wheat, were found to contain all of these T cell epitopes in variable combinations per gene. The differences in epitope composition resulted mainly from point mutations. These substitutions appeared to be genome specific. Our analysis shows that α-gliadin sequences from the three genomes of bread wheat form distinct groups. The four known T cell stimulatory epitopes are distributed non-randomly across the sequences, indicating that the three genomes contribute differently to epitope content. A systematic analysis of all known epitopes in gliadins and glutenins will lead to better understanding of the differences in toxicity among wheat varieties. On the basis of such insight, breeding strategies can be designed to generate less toxic varieties of wheat which may be tolerated by at least part of the CD patient population.
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影响因子：
15.3
作者：
Arentz-Hansen, H;Korner, R;Molberg, O;Quarsten, H;Vader, W;Kooy, Y M;Lundin, K E;Koning, F;Roepstorff, P;Sollid, L M;McAdam, S N
通讯作者：
McAdam, S N
影响因子：
3.1
作者：
Marino, CL;Nelson, JC;Hart, GE
通讯作者：
Hart, GE
影响因子：
5.4
作者：
Anderson, OD;Greene, FC
通讯作者：
Greene, FC
影响因子：
2
作者：
von Büren, M
通讯作者：
von Büren, M
DOI：
10.1084/jem.20012028
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Vader LW;de Ru A;van der Wal Y;Kooy YM;Benckhuijsen W;Mearin ML;Drijfhout JW;van Veelen P;Koning F
通讯作者：
Koning F