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Exploring T cell reactivity to gliadin in young children with newly-diagnosed Celiac disease

Liu, Edwin, McDaniel, Kristen, Case, Stephanie, Yu, Liping, Gerhartz, Bernd, Ostermann, Nils, Fankhauser, Gabriela, Hungerford, Valerie, Zou, Chao, Luyten, Marcel, Seidl, Katherine and Michels, Aaron (2014) Exploring T cell reactivity to gliadin in young children with newly-diagnosed Celiac disease. Autoimmune Diseases, 2014. pp. 1-8. ISSN 0076-6879


Class II major histocompatibility molecules confer disease risk in Celiac disease (CD) by presenting gliadin peptides to CD4 T cells in the small intestine. Deamidation of gliadin peptides by tissue transglutaminase creates immunogenic peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4 T cells. Detecting gliadin specific T cell responses from the peripheral blood has been challenging due to low circulating frequencies and heterogeneity in response to gliadin epitopes. We investigated the peripheral T cell responses to alpha and gamma gliadin epitopes in young children with newly diagnosed and untreated CD. Using peptide/MHC recombinant protein constructs, we are able to robustly stimulate CD4 T cell clones previously derived from intestinal biopsies of CD patients. These recombinant proteins and a panel of α- and γ-gliadin peptides were used to assess T cell responses from the peripheral blood. Proliferation assays using peripheral blood mononuclear cells revealed more CD4 T cell responses to α-gliadin than γ-gliadin peptides with a single deamidated α-gliadin peptide able to identify 60% of CD children. We conclude that α-gliadin epitopes are prevalent in newly diagnosed CD children which have important implications for monitoring disease activity.

Item Type: Article
Keywords: Celiac Disease, DQ2, MHC, HLA, gliadin
Date Deposited: 13 Oct 2015 13:13
Last Modified: 04 Jul 2016 23:45


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