T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease - PubMed (original) (raw)
doi: 10.1038/nsmb.2817. Epub 2014 Apr 28.
Veronica Montserrat 2, Jorge R Mujico 3, Khai Lee Loh 4, Dennis X Beringer 4, Menno van Lummel 3, Allan Thompson 3, M Luisa Mearin 5, Joachim Schweizer 5, Yvonne Kooy-Winkelaar 3, Jeroen van Bergen 3, Jan W Drijfhout 3, Wan-Ting Kan 6, Nicole L La Gruta 6, Robert P Anderson 7, Hugh H Reid 8, Frits Koning 9, Jamie Rossjohn 10
Affiliations
- PMID: 24777060
- DOI: 10.1038/nsmb.2817
T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease
Jan Petersen et al. Nat Struct Mol Biol. 2014 May.
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.
Comment in
- How T cells taste gluten in celiac disease.
Jabri B, Chen X, Sollid LM. Jabri B, et al. Nat Struct Mol Biol. 2014 May;21(5):429-31. doi: 10.1038/nsmb.2826. Epub 2014 Apr 28. Nat Struct Mol Biol. 2014. PMID: 24777059 No abstract available.
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