Wahab Widya A, Šuligoj Tanja, Ellis Julia, Côrtez-Real Beatriz, Ciclitira Paul J
Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.
Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK.
Int J Exp Pathol. 2016 Aug;97(4):303-309. doi: 10.1111/iep.12199. Epub 2016 Sep 23.
Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.
乳糜泻（CD）是一种小肠炎症性疾病。它包括异常的适应性免疫，即HLA - DQ2或DQ8分子将CD毒性麸质肽呈递给麸质敏感的T细胞。一种ω-麦醇溶蛋白/C-大麦醇溶蛋白肽（QPFPQPEQPFPW）和一种黑麦衍生的麦角蛋白肽（QPFPQPQQPIPQ）被认为在CD中具有毒性，因为当用来自CD患者的外周血T细胞克隆进行评估时，它们产生了阳性反应。我们试图使用从CD小肠活检中获得的麸质敏感T细胞系来评估候选肽的免疫原性。我们还试图研究小麦麸质敏感T细胞系与胃蛋白酶 - 胰蛋白酶消化的大麦醇溶蛋白（PTH）和黑麦麦角蛋白（PTS）之间的潜在交叉反应性。合成的候选肽用组织转谷氨酰胺酶（tTG）进行脱酰胺化。通过将CD患者的小肠活检组织与胃蛋白酶 - 胰蛋白酶处理的麸质（PTG）、PTH或PTS以及自体外周血单核细胞（PBMCs）一起培养以进行抗原呈递，从而产生麸质敏感T细胞系。通过掺入³H - 胸腺嘧啶来测量相对细胞增殖，从而确定刺激指数。大多数T细胞系对所研究的肽有反应。小麦麸质敏感T细胞系与醇溶蛋白、麦醇溶蛋白和麦角蛋白肽之间也存在交叉反应性。PTH、PTS、大麦醇溶蛋白和黑麦麦角蛋白衍生的CD抗原敏感T细胞系对PTG显示出阳性刺激。ω-麦醇溶蛋白/C-大麦醇溶蛋白肽和黑麦衍生肽对麸质敏感T细胞系具有免疫原性，并且可能存在于小麦、黑麦和大麦中。可能存在其他共享的CD毒性肽。
