Design of azidoproline containing gluten peptides to suppress CD4+ T-cell responses associated with Celiac disease

Celiac disease is an intestinal disease caused by intolerance for gluten, a common protein in food. A life-long gluten-free diet is the only available treatment. As it is well established that the interaction between proline-rich gluten derived peptides and the human HLA-DQ2 molecules induces immune responses that lead to disease development, we have now designed a series of gluten peptides in which proline residues were replaced by azidoprolines. These peptides were found to bind to HLA-DQ2 with an affinity similar to that of the natural gluten peptide. Moreover, some of these peptides were found to be non-immunogenic and block gluten induced immune responses. These can thus serve as lead compounds for the development of HLA-DQ2 blocker peptides.

Natural gluten peptides were modified by ‘click’ chemistry to yield potential blockers for the HLA-DQ2 protein, which presents immunogenic gluten to T-cells inducing a gluten-specific T-cell response, and thus plays an important role in Celiac disease.Figure optionsDownload as PowerPoint slide