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How T cells taste gluten in celiac disease

Genome-wide association studies have identified genes encoding major histocompatibility (MHC) class II molecules as the single most important predisposing factor for autoimmunity. A new study provides atomic insight into how the antigen receptors of intestinal T cells recognize dietary gluten that drives celiac disease pathogenesis when bound to the MHC class II molecule HLA-DQ2.5, the major genetic risk factor of celiac disease.

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Figure 1: Schematic representation of the TCR interactions with two immunodominant gluten epitopes bound to HLA-DQ2.5 (DQ2.5-glia-α2 and DQ2.5-glia-α1a) reported by Petersen et al.2.
Figure 2: The side chain of the glutamate at P4 in the DQ2.5-glia-α2 epitope forms a salt bridge to the side chain of Lys71β and a hydrogen bond to the side chain of Ser28β in the HLA-DQ2.5 molecule.

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Acknowledgements

The work was supported by grants from the US National Institutes of Health (RO1DK063158, RO1DK58727and P30DK42086) to B.J. and by grants from the Research Council of Norway, the European Research Council and the South-East Norway Regional Health Authority to L.M.S.

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Correspondence to Bana Jabri or Ludvig M Sollid.

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Jabri, B., Chen, X. & Sollid, L. How T cells taste gluten in celiac disease. Nat Struct Mol Biol 21, 429–431 (2014). https://doi.org/10.1038/nsmb.2826

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