A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease
Details
Publication Year 2007-07, Volume 27, Issue #1, Page 23-34
Journal Title
IMMUNITY
Publication Type
Journal Article
Abstract
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.
Publisher
CELL PRESS
Keywords
T-CELL EPITOPE; EUROPEAN GENETICS CLUSTER; SEQUENCE-SPECIFIC PRIMERS; TISSUE TRANSGLUTAMINASE; CRYSTAL-STRUCTURE; MODIFIED PEPTIDE; CEREAL TOXICITY; GLIADIN; GLUTEN; DEAMIDATION
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Creation Date: 2007-07-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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