The Intestinal T Cell Response to α-Gliadin in Adult Celiac Disease Is Focused on a Single Deamidated Glutamine Targeted by Tissue Transglutaminase

• DOI: 10.1084/jem.191.4.603
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Helene Arentz-Hansen; Roman Körner; Øyvind Molberg; Hanne Quarsten; Willemijn Vader; Yvonne M.C. Kooy; Knut E.A. Lundin; Frits Koning; Peter Roepstorff; Ludvig M. Sollid; Stephen N. McAdam
• Keywords: Gliadin; Tissue transglutaminase; Deamidation

The great majority of patients that are intolerant wheat gluten protein due to celiac disease (CD) human histocompatibility leukocyte antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. These two class II molecules chiefly responsible for presentation peptides gluten-specific T cells found only in gut CD but not controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation gliadin plays an important role recognition this food by intestinal cells. Here we have used recombinant antigens demonstrate cell response α-gliadin adult is focused on immunodominant, DQ2-restricted overlap a seven-residue fragment gliadin. We show tTG converts glutamine residue within into glutamic acid process critical recognition. Gluten-specific lines from 16 different all responded one or both these deamidated peptides, indicating epitopes highly relevant pathology. Binding studies showed displayed increased affinity DQ2, molecule known preferentially bind containing negatively charged residues. modified accommodated pockets DQ2 epitopes. results suggest modifications anchor residues lead improved major complex (MHC), altered conformation peptide–MHC may be factor leading responses oral intolerance CD.