Focused B cell response to recurring gluten motif with implications for epitope spreading in celiac disease

作者：Chunyan Zhou, Thomas Østerbye, Emil Bach, Shiva Dahal‐Koirala, Lene S. Høydahl, Øyvind Steinsbø, Jørgen Jahnsen, Knut E. A. Lundin, Søren Buus, Ludvig M. Sollid, Rasmus Iversen · 发表于：Cell Reports · 年份：2022 · DOI：10.1016/j.celrep.2022.111541 · 被引用次数：17 · 研究领域：Celiac Disease Research and Management、Monoclonal and Polyclonal Antibodies Research、Viral Infections and Immunology Research

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.