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

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*

*Corresponding author af dette arbejde

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Abstract

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.

OriginalsprogEngelsk
Artikelnummer111541
TidsskriftCell Reports
Vol/bind41
Udgave nummer4
ISSN2211-1247
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We are thankful to Bjørg Simonsen and Marie K. Johannesen for technical assistance and to Shuo-Wang Qiao for providing the human T cell clone TCC1336.13. The gluten protein databases used for construction of the peptide arrays were compiled by Siri Dørum. Flow cytometry and cell-sorting experiments were conducted at the Flow Cytometry Core Facility, Oslo University Hospital. This work was funded by grants from Stiftelsen KG Jebsen (project SKGJ-MED-017 ) and the University of Oslo World-leading research program on human immunology (WL-IMMUNOLOGY).

Publisher Copyright:
© 2022 The Author(s)

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