The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides

Gastroenterology. 2002 Jun;122(7):1729-37. doi: 10.1053/gast.2002.33606.


Background & aims: Gluten (GLU)-specific T-cell responses in HLA-DQ2 positive adult celiac disease (CD) patients are directed to an immunodominant alpha-gliadin (GLIA) peptide that requires deamidation for T-cell recognition. The aim of the current study was to determine which GLU peptide(s) are involved early in disease.

Methods: We have characterized the GLU-specific T-cell response in HLA-DQ2 positive children with recent onset CD.

Results: We found that 50% of these patients do not respond to the alpha-GLIA peptide but to a diverse set of GLIA and glutenin (GLT) peptides, including 6 novel epitopes. Moreover, individual patients respond to distinct (combinations of) GLU peptides. T-cell cross-reactivity toward homologous GLIA and GLT peptides was observed, which might play a role in the initial spreading of the GLU-specific T-cell response. Although all pediatric patients displayed deamidation-dependent responses, deamidation-independent responses were found in the majority of patients as well. Finally, T-cell responses to 3 of these novel GLU peptides were found in adult CD patients.

Conclusions: The diversity of the GLU-specific T-cell response is far greater than was previously appreciated. Both adult and young CD patients can respond to a diverse repertoire of GLU peptides. The observation that T-cell responses to 3 of the novel peptides are independent of deamidation indicates that T-cell responses can be initiated toward native GLU peptides. The possibility that deamidation drives the GLU response toward immunodominant T-cell stimulatory peptides after disease initiation is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Celiac Disease / immunology*
  • Cell Line
  • Child
  • Child, Preschool
  • Epitopes
  • Gliadin / immunology*
  • Glutens / analogs & derivatives*
  • Glutens / genetics
  • Glutens / immunology*
  • HLA-DQ Antigens / analysis
  • Humans
  • Infant
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • T-Lymphocytes / immunology


  • Epitopes
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Peptide Fragments
  • Glutens
  • Gliadin
  • glutenin