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

Clin Immunol. 2023 Sep 26:109795. doi: 10.1016/j.clim.2023.109795. Online ahead of print.ABSTRACTCeliac 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.PMID:37769786 | DOI:10.1016/j.clim.2023.109795

Source: Clinical Immunology - September 28, 2023 Category: Allergy & Immunology Authors: V Seitz K Gennermann S Elezkurtaj D Groth S Schaper A Dr öge N Lachmann E Berg D Lenze A A K ühl C Husemann K Kleo D Horst V Lennerz S Hennig M Hummel M Schumann Source Type: research