Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa

Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa

Copyright © 2023. Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 256(2023) vom: 31. Nov., Seite 109795
1. Verfasser: Seitz, V (VerfasserIn)
Weitere Verfasser: Gennermann, K, Elezkurtaj, S, Groth, D, Schaper, S, Dröge, A, Lachmann, N, Berg, E, Lenze, D, Kühl, A A, Husemann, C, Kleo, K, Horst, D, Lennerz, V, Hennig, S, Hummel, M, Schumann, M
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Celiac disease Influenza A Refractory celiac disease Somatic recombination T-cell receptor Glutens 8002-80-0 Receptors, Antigen, T-Cell, alpha-beta Receptors, Antigen, T-Cell
Beschreibung
Zusammenfassung:Copyright © 2023. Published by Elsevier Inc.
Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4+ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8+ α/β intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRβ-rearrangements derived from gluten-specific CD4+ T-cells and gluten-triggered peripheral blood CD8+ T-cells. We show, that in addition to TCRs from gluten-specific CD4+ T-cells, TCRs of gluten-triggered CD8+ T-cells are significantly enriched in CeD duodenal tissue samples. TCRβ-rearrangements of gluten-triggered CD8+ T-cells were even more expanded in patients than TCRs from gluten-specific CD4+ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens
Beschreibung:Date Completed 06.11.2023
Date Revised 06.11.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2023.109795