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

Liu, Edwin and McDaniel, Kristen and Case, Stephanie and Yu, Liping and Gerhartz, Bernd and Ostermann, Nils and Fankhauser, Gabriela and Hungerford, Valerie and Zou, Chao and Luyten, Marcel and 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

Abstract

ABSTRACT
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
URI: https://oak.novartis.com/id/eprint/20327

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