KG Jebsen Coeliac Disease Research Center, University of Oslo, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Sci Adv. 2023 Jan 25;9(4):eade5800. doi: 10.1126/sciadv.ade5800.
CD4 T cells specific for cereal gluten proteins are key players in celiac disease (CeD) pathogenesis. While several CeD-relevant gluten T cell epitopes have been identified, epitopes recognized by a substantial proportion of gluten-reactive T cells remain unknown. The identification of such CeD-driving gluten epitopes is important for the food industry and in clinical settings. Here, we have combined the knowledge of a distinct phenotype of gluten-reactive T cells and key features of known gluten epitopes for the discovery of unknown epitopes. We tested 42 wheat gluten-reactive T cell clones, isolated on the basis of their distinct phenotype and with no reactivity to known epitopes, against a panel of synthetic peptides bioinformatically identified from a wheat gluten protein database. We were able to assign reactivity to 10 T cell clones and identified a 9-nucleotide oligomer core region of five previously uncharacterized gliadin/glutenin epitopes. This work represents an advance in the effort to identify CeD-driving gluten epitopes.
针对谷物麸质蛋白的 CD4 T 细胞是乳糜泻（CeD）发病机制中的关键因素。虽然已经确定了几个与 CeD 相关的麸质 T 细胞表位，但仍不清楚大量麸质反应性 T 细胞识别的表位。这些 CeD 驱动的麸质表位的鉴定对于食品工业和临床环境都很重要。在这里，我们结合了对特定麸质反应性 T 细胞表型和已知麸质表位关键特征的了解，用于发现未知表位。我们针对一组合成肽进行了测试，这些肽是从小麦麸质蛋白数据库中通过生物信息学方法鉴定的，共涉及 42 个小麦麸质反应性 T 细胞克隆，这些克隆是基于其独特的表型分离出来的，且对已知表位无反应。我们能够确定 10 个 T 细胞克隆的反应性，并鉴定了五个以前未表征的麦谷蛋白/醇溶谷蛋白表位的 9 个核苷酸寡聚核心区域。这项工作代表了在鉴定 CeD 驱动的麸质表位方面的进展。
