Immunogenic peptides can be detected in whole gluten by transamidating highly susceptible glutamine residues: implication in the search for gluten-­-free cereals.

Tissue transglutaminase (TG2) plays a central role in celiac disease (CD) pathogenesis by strongly enhancing the immunogenicity of gluten, the CD-triggering antigen. By deamidating specific glutamine (Q) residues, TG2 favors the binding of gluten peptides to DQ2/8 molecules and, subsequently, their recognition by cognate T cells. Six peptides were previously identified within wheat gliadin whole extracts by tagging the TG2-susceptible Q residues with monodansylcadaverine (MDC) and nanospray tandem mass spectrometry (nanoESI-MS/MS). The immunogenicity of these peptides was next tested in gliadin-specific T-cell lines established from CD intestinal mucosa. Four peptides, corresponding to known epitopes of ?- and ?-gliadins, induced cell proliferation and interferon (IFN)-? production. Interestingly, one of the two non-T-cell stimulatory peptides corresponded to the 31-49 ?-gliadin peptide implicated in the innate immune activation in CD mucosa. This study describes a strategy for identifying immunogenic gluten peptides potentially relevant for CD pathogenesis in protein extracts from wheat and other edible cereals.