Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes

Gastroenterology. 2017 Sep;153(3):787-798.e4. doi: 10.1053/j.gastro.2017.05.016. Epub 2017 May 20.


Background & aims: Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults.

Methods: We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection.

Results: Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes.

Conclusions: T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease.

Keywords: Autoimmunity; CD4(+) T Cell; PreventCD Study; TG2.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Celiac Disease / immunology*
  • Celiac Disease / pathology*
  • Cell Proliferation
  • Cells, Cultured
  • Child, Preschool
  • Clone Cells
  • Deamination
  • Epitopes / immunology*
  • Female
  • Gliadin / immunology
  • Gliadin / metabolism
  • Gliadin / pharmacology
  • Glutens / immunology*
  • Glutens / metabolism
  • Glutens / pharmacology
  • Humans
  • Immunity, Mucosal
  • Intestinal Mucosa / immunology*
  • Intestine, Small / pathology
  • Male
  • Middle Aged
  • Peptides / immunology
  • Primary Cell Culture
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Epitopes
  • Peptides
  • Glutens
  • Gliadin