4ozh

Publication Abstract from PubMed

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-alpha1a and DQ2.5-glia-alpha2. We determined the ternary structures of four distinct biased TCRs specific for those epitopes. All three TCRs specific for DQ2.5-glia-alpha2 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 CDR3beta loop acted as the lynchpin within this common docking footprint. Although the TCRs specific for DQ2.5-glia-alpha1a and DQ2.5-glia-alpha2 docked similarly, their interactions with the respective gliadin determinants differed markedly, thereby providing a basis for epitope specificity.

T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease.,Petersen J, Montserrat V, Mujico JR, Loh KL, Beringer DX, van Lummel M, Thompson A, Mearin ML, Schweizer J, Kooy-Winkelaar Y, van Bergen J, Drijfhout JW, Kan WT, La Gruta NL, Anderson RP, Reid HH, Koning F, Rossjohn J Nat Struct Mol Biol. 2014 May;21(5):480-8. doi: 10.1038/nsmb.2817. Epub 2014 Apr , 28. PMID:24777060^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.