A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease
- Henderson, KN; Tye-Din, JA; Reid, HH; Chen, Z; Borg, NA; Beissbarth, T; Tatham, A; Mannering, SI; Purcell, AW; Dudek, NL; van Heel, DA; McCluskey, J; Rossjohn, J; Anderson, RP;
Publication Year 2007-07, Volume 27, Issue #1, Page 23-34
- Journal Title
- Publication Type
- Journal Article
- The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual.
- CELL PRESS
- T-CELL EPITOPE; EUROPEAN GENETICS CLUSTER; SEQUENCE-SPECIFIC PRIMERS; TISSUE TRANSGLUTAMINASE; CRYSTAL-STRUCTURE; MODIFIED PEPTIDE; CEREAL TOXICITY; GLIADIN; GLUTEN; DEAMIDATION
- Publisher's Version
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Creation Date: 2007-07-01 12:00:00Last Modified: 0001-01-01 12:00:00