The findings support a theory recently posited by Kappler, Eisenbarth, and Brian Stadinski, PhD, of Harvard Medical School. They believe that poorly presented peptides are more likely to cause diabetes and other autoimmune diseases, because they allow autoimmune T cells to escape deletion. Once they begin circulating in the body, these T cells are stimulated when they encounter high concentrations of the peptide or peptides that have been processed differently outside the thymus.

"This is the third time that a specific peptide and its binding register have been associated with autoimmune disease," said Kappler. "All three have been peptides that are weakly bound to the MHCII molecule."

These findings have a direct link to human disease. Development of the type I diabetes in humans is also associated with a particular form of the MHCII molecule, which has a binding pattern similar to the one in mice. Kappler and Eisenbarth plan to see if T cells associated with diabetes in humans also bind the same insulin peptide in the same register as the mouse version.

If the peptide does stimulate T cells associated with diabetes in humans, the discovery would suggest potential diagnostic and therapeutic strategies. Detecting and/or blocking that peptide-MHC complex with an antibody could detect early onset of the disease and might be able to slow or block progression of the disease.

Source: National Jewish Health