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

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.

PubMed Disclaimer

Comment in

Similar articles

Cited by

References

    1. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D593-7 - PubMed
    1. J Immunol. 2011 Sep 15;187(6):3064-71 - PubMed
    1. Sci Transl Med. 2012 Apr 4;4(128):128ra42 - PubMed
    1. Nat Rev Immunol. 2009 Dec;9(12):858-70 - PubMed
    1. Immunol Rev. 2012 Nov;250(1):32-48 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources