KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China.
Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Cell Rep. 2022 Oct 25;41(4):111541. doi: 10.1016/j.celrep.2022.111541.
Antibodies to deamidated gluten peptides are accurate diagnostic markers of celiac disease. However, binding of patient antibodies to all possible gluten epitopes has not previously been investigated. Here, we assess serum antibody specificity across the gluten proteome by use of high-density peptide arrays. We confirm the importance of deamidation for antibody binding, and we show that the response is remarkably focused on the known epitope QPEQPFP (where E results from deamidation of Q). In addition, we describe an epitope in native (non-deamidated) gluten, QQPEQII (where E is gene encoded), which is associated with both B cell and T cell reactivity. Antibodies to this native epitope are cross-reactive with the major deamidated epitope due to recognition of the shared PEQ motif. Since cross-reactive B cells can present peptides to different gluten-specific T cells, we propose that such B cells play a role in epitope spreading by engaging T cells with multiple specificities.
针对脱酰胺麸质肽的抗体是乳糜泻的准确诊断标志物。然而，以前尚未研究过患者抗体与所有可能的麸质表位的结合情况。在这里，我们通过使用高密度肽阵列来评估整个麸质蛋白质组中的血清抗体特异性。我们证实了脱酰胺对抗体结合的重要性，并且我们表明，该反应非常集中在已知表位 QPEQPFP（其中 E 来自 Q 的脱酰胺）上。此外，我们描述了一个存在于天然（非脱酰胺）麸质中的表位，QQPEQII（其中 E 是基因编码的），它与 B 细胞和 T 细胞的反应性均有关。由于识别共同的 PEQ 基序，针对该天然表位的抗体与主要脱酰胺表位发生交叉反应。由于交叉反应性 B 细胞可以将肽呈递给不同的特定于麸质的 T 细胞，因此我们提出，这些 B 细胞通过与多种特异性的 T 细胞结合来发挥在表位扩展中的作用。
