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

Abstract

Summary 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.