Abstract
Purpose
Celiac disease (CD) is a permanent intolerance to wheat prolamins and related proteins displayed by genetically susceptible individuals. Blocking or modulation of CD-specific T cell response by altered prolamin peptides are currently considered as a potential alternative to the only effective therapy of CD based on a life-long gluten-free diet. Two prolamin peptides, the 9-mer ASRVAPGQQ and the 10-mer GTVGVAPGQQ sequences, were identified by mass spectrometry in the peptic/tryptic digest of prolamins (PTP) from durum wheat (Triticum turgidum ssp. durum) cv. Adamello, and investigated for their ability to preclude the stimulation of CD-specific mucosal T cells by gluten proteins.
Methods
Gluten-specific polyclonal intestinal T cell lines from five CD children (mean age 5 years) were exposed to 50 μg/ml of a deamidated PTP from whole flour of common wheat (T. aestivum) cv. San Pastore, and tested for proliferation and production of interferon-γ (INF-γ) and interleukin 10 (IL-10). The same experiment was performed in the presence of 20 μg/ml of the 9-mer or the 10-mer peptide.
Results
T cells exposed to PTP showed a threefold increase in proliferation and INF-γ production, and a significant (P ≤ 0.05) reduction in IL-10 secretion as compared with control cells incubated with the culture medium. Addition of either the 9-mer or the 10-mer peptide to PTP downregulated T cell proliferation and INF-γ production, and caused a significant (P ≤ 0.05) increase in IL-10 secretion.
Conclusions
The T cell reactivity elicited by PTP is precluded by both the 9-mer and the 10-mer sequence, suggesting that over-expression of these proteolytically stable peptides may result in a wheat flour with reduced toxicity for CD patients.
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De Vincenzi, M., Vincentini, O., Di Nardo, G. et al. Two prolamin peptides from durum wheat preclude celiac disease-specific T cell activation by gluten proteins. Eur J Nutr 49, 251–255 (2010). https://doi.org/10.1007/s00394-009-0080-4
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DOI: https://doi.org/10.1007/s00394-009-0080-4