Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2020 Dec 6;21(23):9301. doi: 10.3390/ijms21239301.
Gluten fragments released in gut of celiac individuals activate the innate or adaptive immune systems. The molecular mechanisms associated with the adaptive response involve a series of immunodominant gluten peptides which are mainly recognized by human leucocyte antigen (HLA)-DQ2.5 and HLA-DQ8. Other peptides, such as A-gliadin P31-43, are not recognized by HLA and trigger innate responses by several routes not yet well detailed. Among the gluten fragments known to be active in Celiac disease, here we focus on the properties of all gluten peptides with known tri-dimensional structure either those locked into HLA-DQ complexes whose crystals were X-ray analyzed or characterized in solution as free forms. The aim of this work was to find the structural reasons why some gluten peptides prompt the adaptive immune systems while others do not, by apparently involving just the innate immune routes. We propose that P31-43 is a non-adaptive prompter because it is not a good ligand for HLA-DQ. Even sharing a similar ability to adopt polyproline II structure with the adaptive ones, the way in which the proline residues are located along the sequence disfavors a productive P31-43-HLA-DQ binding.
在乳糜泻患者的肠道中释放的麸质片段会激活先天或适应性免疫系统。与适应性反应相关的分子机制涉及一系列主要被人类白细胞抗原 (HLA)-DQ2.5 和 HLA-DQ8 识别的免疫优势麸质肽。其他肽，如 A-醇溶蛋白 P31-43，不能被 HLA 识别，并通过尚未详细阐明的几种途径触发先天反应。在已知在乳糜泻中起作用的麸质片段中，我们在这里重点关注所有具有已知三维结构的麸质肽的特性，这些肽要么锁定在 HLA-DQ 复合物中，其晶体已通过 X 射线分析，要么以游离形式在溶液中进行了表征。这项工作的目的是找到一些麸质肽为什么会引发适应性免疫系统而另一些则不会的结构原因，因为它们似乎只涉及先天免疫途径。我们提出 P31-43 是一种非适应性启动子，因为它不是 HLA-DQ 的良好配体。即使与适应性肽具有类似的采用多脯氨酸 II 结构的能力，脯氨酸残基在序列中的位置也不利于产生 P31-43-HLA-DQ 结合。
