The only generally accepted treatment of coeliac disease (CD) is a lifelong gluten-free diet. Wheat gluten proteins include gliadins, low and high molecular weight glutenins. However, we have found significant structural variations within these protein families among different cultivars. To determine which structural motifs might be less toxic than others, we assessed five variants of α-gliadin immunodominant CD-toxic peptides synthesised as 16mers in CD T cell stimulation assays with gluten-sensitive T cell lines generated from duodenal biopsies from CD-affected individuals. The peptides harboured the overlapping T cell epitopes DQ 2.5-glia-α-2 and naturally occurring variants that differed in certain amino acids (AA). The results revealed that introduction of two selected AA substitutions in α-gliadin peptides reduced immunogenicity. A peptide with three AA substitutions involving two glutamic acids (E) and one glutamine residue (G) revealed the peptide was negative in 5:5 samples. We used CD small-intestinal organ culture to assess CD toxicity that revealed two peptides with selected substitution of both glutamic acid (E) and proline (P) residues abrogated evidence of CD toxicity.

腹腔疾病（CD）唯一公认的治疗方法是终生无麸质饮食。小麦面筋蛋白包括麦醇溶蛋白，低和高分子量的谷蛋白。但是，我们发现这些蛋白家族在不同品种之间存在明显的结构变异。为了确定哪些结构基序的毒性可能比其他结构基序低，我们评估了CD-T细胞刺激测定中以16mer形式合成的α-麦醇溶蛋白免疫优势CD-毒性肽的五个变体，这些变体是由受CD影响的个体的十二指肠活检产生的面筋敏感T细胞系。肽具有重叠的T细胞表位DQ 2.5-胶质-α-2和天然存在的变体，其中某些氨基酸（AA）不同。结果表明，在α-麦醇溶蛋白肽中引入两个选定的AA替代物会降低免疫原性。具有3个AA取代的肽，涉及两个谷氨酸（E）和一个谷氨酰胺残基（G），表明该肽在5：5样品中呈阴性。我们使用CD小肠器官培养来评估CD毒性，该结果揭示了两个具有谷氨酸（E）和脯氨酸（P）残基的选择性取代的肽消除了CD毒性的证据。