6U3N

LS2.8/3.15 - DQ2-P.fluor-alpha1a complex

Summary for 6U3N

• Entry DOI: 10.2210/pdb6u3n/pdb
• Descriptor: T-CELL RECEPTOR, LS2.8/3.15 alpha, T-CELL RECEPTOR, LS2.8/3.15 beta, MHC class II HLA-DQ-alpha chain, ... (7 entities in total)
• Functional Keywords: immune complex, celiac disease, gliadin epitope, tcr cross-reactivity, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 97892.85

Authors

Petersen, J.,Rossjohn, J. (deposition date: 2019-08-22, release date: 2019-12-18, Last modification date: 2024-11-13)

Primary citation

Petersen, J.,Ciacchi, L.,Tran, M.T.,Loh, K.L.,Kooy-Winkelaar, Y.,Croft, N.P.,Hardy, M.Y.,Chen, Z.,McCluskey, J.,Anderson, R.P.,Purcell, A.W.,Tye-Din, J.A.,Koning, F.,Reid, H.H.,Rossjohn, J.
T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease.
Nat.Struct.Mol.Biol., 27:49-61, 2020

PubMed Abstract: 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.

PubMed: 31873306
DOI: 10.1038/s41594-019-0353-4

Experimental method

X-RAY DIFFRACTION (2.8 Å)