Exploring T cell reactivity to gliadin in young children with newly diagnosed celiac disease.
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 it is possible to detect T cell responses without a gluten challenge or in vitro stimulus other than antigen, when measuring proliferative responses.
Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Mail Stop A140, 1775 Aurora Court, Aurora, CO 80045, USA.
Edwin
E
Liu
Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Mail Stop A140, 1775 Aurora Court, Aurora, CO 80045, USA.
Kristen
K
McDaniel
Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Mail Stop A140, 1775 Aurora Court, Aurora, CO 80045, USA.
Stephanie
S
Case
Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Mail Stop A140, 1775 Aurora Court, Aurora, CO 80045, USA.
Liping
0000-0003-0664-2154
L
Yu
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Bernd
B
Gerhartz
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Nils
N
Ostermann
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Gabriela
G
Fankhauser
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Valerie
V
Hungerford
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Chao
C
Zou
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Marcel
M
Luyten
Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Katherine J
KJ
Seidl
Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Mail Stop A140, 1775 Aurora Court, Aurora, CO 80045, USA.
Aaron W
AW
Michels