Introduction: Deamidated gliadin peptides (DGP), which are generated from a complex of tissue transglutaminase (tTG) and gliadin peptides, induce strong proliferative T cell responses in active Celiac disease. Previously, we demonstrated that 12-amino-acid-long synthetic peptides that model the tTG-DGP complex (mimetics) may be useful for predicting which treated CeD patients will fail to heal. We hypothesize that specific mimetics of the tTG/gliadin complex, but not all mimetics, can induce T cell proliferation.
Methods: Using AEoDQ8 mice and NODAboDQ8 mice, we tested a subset of 7 CeD mimetics for their ability to induce T cell proliferation. The 12AA peptides were created by randomly inserting 3AA sequences derived from tTG and DGP. 7 mimetics were chosen from hundreds that were found to bind to Celiac sera, specifically sera obtained from DQ2+ and/or DQ8+ CeD patients. dDQ8, a gliadin derived peptide that we previously had shown to induce a strong T cell proliferation in the NODABoDQ8 mice, was used as a positive control. Human Clip II peptide and media only were used as negative controls.
Results Two mimetics (SEQ130 and SEQ447) induced T cell proliferation in the AeoDQ8 mice and/or NODAboDQ8 mice, comparable to that of dDQ8 alone. The third mimetic (SEQ8) induced a low level of T cell proliferation. The other 4 mimetics tested did not incuce T cell proliferation in the two DQ8+ mouse lines. Anti DQ antibody reduced the in vitro proliferation induced by the three mimetics.
Conclusions: Two of the 7 mimetics tested induce strong T cell proliferation in the AeoDQ8 and/or NODABoDQ8 mice, and a third mimetic induced a low level of T cell proliferation. The other 4 mimetics tested did not induce T cell proliferation in the DQ8 transgenic mice, suggesting that only specific sites in the tTG/gliadin complex can induce T cell proliferation.