A quantitative analysis of transglutaminase 2-mediated deamidation of gluten peptides: implications for the T-cell response in celiac disease.

Celiac disease develops in genetically predisposed individuals as the result of an inappropriate intestinal immune response to dietary gluten proteins. T cells present in the intestine of celiac patients recognize gluten peptides in the context of HLA-DQ2 or -DQ8 molecules. Notably, T-cell recognition is increased after these peptides have been deamidated by the enzyme transglutaminase 2. Several T-cell epitopes of gluten exist, and most of these epitopes derive from the alcohol-soluble gliadin fraction. For some of these epitopes, specific T cells can be isolated from intestinal biopsies from nearly all patients, whereas for others, T-cell reactivity could be demonstrated in only a few patients. One reason for this observation could be that the rate of transglutaminase 2 (TG2)-mediated deamidation significantly differs between these peptides, resulting in different amounts of epitopes generated in vivo. In this study, we established a quantitative, mass spectrometry-based approach to measure the kinetics...