Structural bases of T cell antigen receptor recognition in celiac disease

Journal article

Celiac disease (CeD) is a human leukocyte antigen (HLA)-linked autoimmune-like disorder that is triggered by the ingestion of gluten or related storage proteins. The majority of CeD patients are HLA-DQ2.5⁺, with the remainder being either HLA-DQ8⁺ or HLA-DQ2.2⁺. Structural studies have shown how deamidation of gluten epitopes engenders binding to HLA-DQ2.5/8, which then triggers an aberrant CD4⁺ T cell response. HLA tetramer studies, combined with structural investigations, have demonstrated that repeated patterns of TCR usage underpins the immune response to some HLADQ2.5/8 restricted gluten epitopes, with distinct TCR motifs representing common landing pads atop the HLA–gluten complexes. Structural studies have provided insight into TCR specificity and cross-reactivity towards gluten epitopes, as well as cross-reactivity to bacterial homologues of gluten epitopes, suggesting that environmental factors may directly play a role in CeD pathogenesis. Collectively, structural immunology-based studies in the CeD axis may lead to new therapeutics/diagnostics to treat CeD, and also serve as an exemplar for other T cell mediated autoimmune diseases.

Authors: Ciacchi, L; Reid, HH; Rossjohn, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Current Opinion in Structural Biology
• Volume: 74
• Article number: 102349
• Publication date: 2022-03-07
• Acceptance date: 2022-01-30
• DOI: 10.1016/j.sbi.2022.102349
• EISSN: 1879-033X
• ISSN: 0959-440X
• Language: English