Petersen, Jan, Montserrat, Veronica, Mujico, Jorge R., Loh, Khai Lee, Beringer, Dennis X., van Lummel, Menno, Thompson, Allan, Mearin, M Luisa, Schweizer, Joachim, Kooy-Winkelaar, Yvonne, van Bergen, Jeroen, Drijfhout, Jan W., Kan, Wan-Ting, La Gruta, Nicole L, Anderson, Robert P., Reid, Hugh H., Koning, Frits and Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 2014. T-cell receptor recognition of HLA-DQ2–gliadin complexes associated with celiac disease. Nature Structural and Molecular Biology 21 (5) , pp. 480-488. 10.1038/nsmb.2817 |
Abstract
Celiac disease is a T cell–mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epitopes from wheat gliadin, DQ2.5-glia-α1a and DQ2.5-glia-α2. We determined the ternary structures of four distinct biased TCRs specific for those epitopes. All three TCRs specific for DQ2.5-glia-α2 docked centrally above HLA-DQ2, which together with mutagenesis and affinity measurements provided a basis for the biased TCR usage. A non–germline encoded arginine residue within the CDR3β loop acted as the lynchpin within this common docking footprint. Although the TCRs specific for DQ2.5-glia-α1a and DQ2.5-glia-α2 docked similarly, their interactions with the respective gliadin determinants differed markedly, thereby providing a basis for epitope specificity.
Item Type: | Article |
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Date Type: | Published Online |
Status: | Published |
Schools: | Medicine |
Subjects: | R Medicine > R Medicine (General) |
Uncontrolled Keywords: | immunology |
Publisher: | Nature Publishing Group |
ISSN: | 1545-9993 |
Date of Acceptance: | 28 March 2014 |
Last Modified: | 01 Nov 2022 10:14 |
URI: | https://orca.cardiff.ac.uk/id/eprint/90758 |
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