Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease

Petersen, Jan, Ciacchi, Laura, Tran, Mai T., Loh, Khai Lee, Kooy-Winkelaar, Yvonne, Croft, Nathan P., Hardy, Melinda Y., Chen, Zhenjun, McCluskey, James, Anderson, Robert P., Purcell, Anthony W., Tye-Din, Jason A., Koning, Frits, Reid, Hugh H. and Rossjohn, Jamie 2020. T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease. Nature Structural and Molecular Biology 27 (1) , pp. 49-61. 10.1038/s41594-019-0353-4

PDF - Accepted Post-Print Version
Download (3MB) | Preview


The human leukocyte antigen (HLA) locus is strongly associated with T cell-mediated autoimmune disorders. HLA-DQ2.5-mediated celiac disease (CeD) is triggered by the ingestion of gluten, although the relative roles of genetic and environmental risk factors in CeD is unclear. Here we identify microbially derived mimics of gliadin epitopes and a parental bacterial protein that is naturally processed by antigen-presenting cells and activated gliadin reactive HLA-DQ2.5-restricted T cells derived from CeD patients. Crystal structures of T cell receptors in complex with HLA-DQ2.5 bound to two distinct bacterial peptides demonstrate that molecular mimicry underpins cross-reactivity toward the gliadin epitopes. Accordingly, gliadin reactive T cells involved in CeD pathogenesis cross-react with ubiquitous bacterial peptides, thereby suggesting microbial exposure as a potential environmental factor in CeD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1545-9993
Date of First Compliant Deposit: 31 January 2020
Date of Acceptance: 18 November 2019
Last Modified: 20 Jan 2021 06:24

Citation Data

Cited 6 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics