Tighe M R, Ciclitira P J
Division of Pharmacology, United Medical and Dental Schools of Guy's Hospital, London, UK.
Baillieres Clin Gastroenterol. 1995 Jun;9(2):211-30. doi: 10.1016/0950-3528(95)90029-2.
Work continues to progress in the unravelling of the molecular interactions involved in the pathogenesis of coeliac disease. The immunogenetics of the disease implicate certain HLA DQ alleles as necessary for subsequent disease development. These HLA molecules have been shown to be necessary in the binding and presentation of gliadin peptides to antigen-specific T cells. Current work is examining the precise HLA-antigen interaction that may lead to the development of antigen-blocking agents. The isolation of antigen-specific T cells has led to the confirmation of a toxic T-cell epitope of the gliadin protein (residues 31-49) and it would appear likely that additional toxic epitopes may be similarly characterized in the near future. No common TCR motifs have so far been detected, although these may become apparent as this work progresses. The gliadin peptide sequence, residues 31-49, has now been demonstrated to be toxic in vivo. Additional toxic T-cell epitopes may also be present within gliadins, but this identification of a toxic gliadin sequence for the first time raises the possibility of future manipulation of the wheat genome (and other toxic cereals) that could lead to the development of new graminae cereals with the properties of wheat, but which do not induce toxicity in patients with coeliac disease.
在解开乳糜泻发病机制中所涉及的分子相互作用方面，研究工作仍在继续推进。该疾病的免疫遗传学表明，某些HLA DQ等位基因是后续疾病发展所必需的。这些HLA分子已被证明在将麦醇溶蛋白肽结合并呈递给抗原特异性T细胞的过程中是必需的。目前的研究正在考察可能导致抗原阻断剂研发的精确HLA - 抗原相互作用。抗原特异性T细胞的分离已证实了麦醇溶蛋白的一个毒性T细胞表位（第31 - 49位氨基酸残基），而且在不久的将来可能会类似地鉴定出更多毒性表位。尽管随着这项工作的进展这些共有TCR基序可能会变得明显，但目前尚未检测到共同的TCR基序。现已证明麦醇溶蛋白肽序列（第31 - 49位氨基酸残基）在体内具有毒性。麦醇溶蛋白中可能还存在其他毒性T细胞表位，但首次鉴定出毒性麦醇溶蛋白序列增加了未来对小麦基因组（以及其他有毒谷物）进行操控的可能性，这可能会培育出具有小麦特性但不会对乳糜泻患者诱发毒性的新型禾本科谷物。
