Elevated CD8 T cell responses in type 1 diabetes patients to a 13 amino acid coeliac-active peptide from α-gliadin

Clin Exp Immunol. 2014 Feb;175(2):167-71. doi: 10.1111/cei.12203.

Abstract

Some type 1 diabetes (T1D) patients have been reported to exhibit T cell reactivity to wheat gluten. We tested the hypothesis that this T cell reactivity could be abolished by using prolyl-endopeptidase (PEP), an enzyme that cleaves peptide bonds after proline. Peripheral blood mononuclear cells (PBMCs) were isolated from T1D patients and healthy controls. PBMCs were stimulated with a peptic-tryptic digest of wheat gluten; a peptic-tryptic-PEP digest of wheat gluten; and a 13 amino acid peptide from wheat gluten. Fluorescent-labelled antibodies to CD3, CD4 and CD8 cell marker proteins were utilized to determine proliferative responses of CD3, CD4 and CD8 T cells. There were no significant differences in proliferative responses of CD3 or CD4 T cells to the wheat gluten antigens. A significantly higher proportion of CD8(+) T cells from T1D patients proliferated in the presence of the 13 amino acid peptide than when challenged with the peptic-tryptic or the peptic-tryptic-PEP digests of wheat gluten. PEP treatment had no significant effect on CD8 T cell reactivity to the peptic-trytic digest of wheat gluten. Our results suggest that wheat gluten-derived peptides, containing ≤ 13 amino acids, may evoke T cell responses in T1D patients.

Keywords: T cell responses; peptides; prolyl-endopeptidase; type 1 diabetes; wheat gluten.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • CD3 Complex / immunology
  • CD4 Antigens / immunology
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Endopeptidases / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Gliadin / immunology*
  • Glutens / immunology*
  • Glutens / metabolism
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • Peptides / immunology*
  • Peptides / metabolism
  • Young Adult

Substances

  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Peptides
  • Glutens
  • Gliadin
  • Endopeptidases