TY  - JOUR
AU  - Seitz, V.
AU  - Gennermann, K.
AU  - Elezkurtaj, S.
AU  - Groth, D.
AU  - Schaper, S.
AU  - Dröge, A.
AU  - Lachmann, N.
AU  - Berg, E.
AU  - Lenze, D.
AU  - Kühl, A. A.
AU  - Husemann, Cora
AU  - Kleo, K.
AU  - Horst, D.
AU  - Lennerz, V.
AU  - Hennig, S.
AU  - Hummel, Manuela
AU  - Schumann, M.
TI  - Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa.
JO  - Clinical immunology
VL  - 256
SN  - 1521-6616
CY  - Orlando, Fla.
PB  - Academic Press
M1  - DKFZ-2023-01969
SP  - 109795
PY  - 2023
N1  - Volume 256, November 2023, 109795
AB  - 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.
KW  - Celiac disease (Other)
KW  - Influenza A (Other)
KW  - Refractory celiac disease (Other)
KW  - Somatic recombination (Other)
KW  - T-cell receptor (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37769786
DO  - DOI:10.1016/j.clim.2023.109795
UR  - https://inrepo02.dkfz.de/record/283204
ER  -