Epitopes described in "Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease."

Article Authors:Sophie E Broughton; Jan Petersen; Alex Theodossis; Stephen W Scally; Khai Lee Loh; Allan Thompson; Jeroen van Bergen; Yvonne Kooy-Winkelaar; Kate N Henderson; Travis Beddoe; Jason A Tye-Din; Stuart I Mannering; Anthony W Purcell; James McCluskey; Robert P Anderson; Frits Koning; Hugh H Reid; Jamie Rossjohn
Article Title:Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease.
Reference Detail
Reference ID:1025186
Abstract:Celiac disease is a human leukocyte antigen (HLA)-DQ2- and/or DQ8-associated T cell-mediated disorder that is induced by dietary gluten. Although it is established how gluten peptides bind HLA-DQ8 and HLA-DQ2, it is unclear how such peptide-HLA complexes are engaged by the T cell receptor (TCR), a recognition event that triggers disease pathology. We show that biased TCR usage (TRBV9(∗)01) underpins the recognition of HLA-DQ8--I-gliadin. The structure of a prototypical TRBV9(∗)01-TCR-HLA-DQ8--I-gliadin complex shows that the TCR docks centrally above HLA-DQ8--I-gliadin, in which all complementarity-determining region- (CDR) loops interact with the gliadin peptide. Mutagenesis at the TRBV9(∗)01-TCR-HLA-DQ8--I-gliadin interface provides an energetic basis for the V bias. Moreover, CDR3 diversity accounts for TRBV9(∗)01(+) TCRs exhibiting differing reactivities toward the gliadin epitopes at various deamidation states. Accordingly, biased TCR usage is an important factor in the pathogenesis of DQ8-mediated celiac disease.
Affiliations:The Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
Reference Type:Literature
PubMed ID:23063329
Journal Volume:37
Article Pages:611-21
Journal ISSN:1074-7613
Article Chemical List:Epitopes, T-Lymphocyte;HLA-DQ Antigens;HLA-DQ8 antigen;Peptide Fragments;Receptors, Antigen, T-Cell;Gliadin
Article MeSH List:Amino Acid Sequence; Celiac Disease(immunology); Epitopes, T-Lymphocyte(immunology); Gliadin(immunology); HLA-DQ Antigens(chemistry; immunology); Humans; Models, Molecular; Molecular Sequence Data; Peptide Fragments(immunology); Protein Interaction Domains and Motifs; Receptors, Antigen, T-Cell(chemistry; immunology)
Curation Last Updated:2014-10-03 22:48:39