Journal article
A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease
YT Ting, S Dahal-Koirala, HSK Kim, SW Qiao, RS Neumann, KEA Lundin, J Petersen, HH Reid, LM Sollid, J Rossjohn
Proceedings of the National Academy of Sciences of the United States of America | Published : 2020
Abstract
The highly homologous human leukocyte antigen (HLA)-DQ2 molecules, HLA-DQ2.5 and HLA-DQ2.2, are implicated in the pathogenesis of celiac disease (CeD) by presenting gluten peptides to CD4+ T cells. However, while HLA-DQ2.5 is strongly associated with disease, HLA-DQ2.2 is not, and the molecular basis underpinning this differential disease association is unresolved. We here provide structural evidence for how the single polymorphic residue (HLA-DQ2.5-Tyr22α and HLA-DQ2.2-Phe22α) accounts for HLADQ2.2 additionally requiring gluten epitopes possessing a serine at the P3 position of the peptide. In marked contrast to the biased T cell receptor (TCR) usage associated with HLA-DQ2.5–mediated CeD, ..
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Awarded by Australian Research Council
Funding Acknowledgements
This research was supported by the National Health and Medical Research Council (Australia) and Australian Research Council (ARC) (J.R.); by the South-Eastern Norway Regional Health Authority Projects 2011050 and 2015009; Research Council of Norway Project 179573/V40 through the Centre of Excellence funding scheme, and Project 233885; and the Stiftelsen Kristian Gerhard Jebsen Project SKGJ-MED-017 (to L.M.S.). J.R. is supported by an ARC Australian Laureate Fellowship. We thank Khai Lee Loh, Mai Tran, and Bjorg Simonsen for their excellent technical assistance. The protein crystal X-ray diffraction data were collected on MX2 beamline at the Australian Synchrotron facility, Melbourne, Australia.