Focused B cell response to recurring gluten motif with implications for epitope spreading in celiac disease
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Focused B cell response to recurring gluten motif with implications for epitope spreading in celiac disease. / Zhou, Chunyan; Østerbye, Thomas; Bach, Emil; Dahal-Koirala, Shiva; Høydahl, Lene S.; Steinsbø, Øyvind; Jahnsen, Jørgen; Lundin, Knut E.A.; Buus, Søren; Sollid, Ludvig M.; Iversen, Rasmus.
In: Cell Reports, Vol. 41, No. 4, 111541, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Focused B cell response to recurring gluten motif with implications for epitope spreading in celiac disease
AU - Zhou, Chunyan
AU - Østerbye, Thomas
AU - Bach, Emil
AU - Dahal-Koirala, Shiva
AU - Høydahl, Lene S.
AU - Steinsbø, Øyvind
AU - Jahnsen, Jørgen
AU - Lundin, Knut E.A.
AU - Buus, Søren
AU - Sollid, Ludvig M.
AU - Iversen, Rasmus
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - antibodies
KW - celiac disease
KW - CP: Immunology
KW - cross-reactivity
KW - epitope spreading
KW - gluten
KW - peptide arrays
KW - plasma cells
KW - T cell-B cell collaboration
U2 - 10.1016/j.celrep.2022.111541
DO - 10.1016/j.celrep.2022.111541
M3 - Journal article
C2 - 36288703
AN - SCOPUS:85140401206
VL - 41
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 4
M1 - 111541
ER -
ID: 324317852