%0 Journal Article
%A Seitz, V.
%A Gennermann, K.
%A Elezkurtaj, S.
%A Groth, D.
%A Schaper, S.
%A Dröge, A.
%A Lachmann, N.
%A Berg, E.
%A Lenze, D.
%A Kühl, A. A.
%A Husemann, Cora
%A Kleo, K.
%A Horst, D.
%A Lennerz, V.
%A Hennig, S.
%A Hummel, Manuela
%A Schumann, M.
%T Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa.
%J Clinical immunology
%V 256
%@ 1521-6616
%C Orlando, Fla.
%I Academic Press
%M DKFZ-2023-01969
%P 109795
%D 2023
%Z Volume 256, November 2023, 109795
%X 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.
%K Celiac disease (Other)
%K Influenza A (Other)
%K Refractory celiac disease (Other)
%K Somatic recombination (Other)
%K T-cell receptor (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37769786
%R 10.1016/j.clim.2023.109795
%U https://inrepo02.dkfz.de/record/283204