Journal article
T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease
J Petersen, V Montserrat, JR Mujico, KL Loh, DX Beringer, M Van Lummel, A Thompson, ML Mearin, J Schweizer, Y Kooy-Winkelaar, J Van Bergen, JW Drijfhout, WT Kan, NL La Gruta, RP Anderson, HH Reid, F Koning, J Rossjohn
Nature Structural and Molecular Biology | Published : 2014
DOI: 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-α 1a and DQ2.5-glia-α 2. We determined the ternary structures of four distinct biased TCRs specific for those epitopes. All three TCRs specific for DQ2.5-glia-α 2 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 t..
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Awarded by Dutch government
Funding Acknowledgements
We thank the staff of the Monash crystallization facility and the Australian Synchrotron for assistance with crystallization and data collection, respectively. This work was supported by the Australian Research Council, the National Health and Medical Research Council (NHMRC) of Australia, the Celiac Disease Consortium and an Innovative Cluster approved by The Netherlands Genomics Initiative and was funded in part by the Dutch government (grant BSIK03009). We thank J. Tye-Din for assistance. J.R. is supported by an Australia Fellowship from the NHMRC.