Scientists Have Found the Peptide Trigger for Type 1 Diabetes in Animal Tests

Researchers from the National Jewish Health and University of Colorado Anschutz Medical Campus have found a specific protein fragment, or peptide, that stimulates an immune system attack resulting in diabetes. Their experiments in mice contradict conventional wisdom about such peptides and support work by scientists studying autoimmune diseases.

To understand what the researchers found, you have to take the molecular view. A specific molecule, named MHCII, communicates with the immune system by presenting various peptides, which the system learns to attack.

Earlier studies had found an insulin fragment that hooked up with MHCII. But scientists didn’t know exactly how that insulin fragment connected to the molecule (like a couple of Lego blocks, there are several ways the two could attach). They also didn’t know how it stimulated the immune system T cells that ultimately attack. That’s the peptide’s job.

Conventional wisdom held that the peptide resulting from the tightest connection of fragment and molecule triggered diabetes. The scientists found, however, that the weakest bond produced the problematic peptide.

“Although scientists have been closing in on the cause of type 1 diabetes, this is the first time that anyone has identified exactly what T cells recognize when they initiate an autoimmune attack in diabetes,” said Dr. George Eisenbarth, a co-author of the paper, in a news article.  The findings appear in the new issue of Proceedings of the National Academy of Sciences.

The findings corroborate a theory by Eisenbarth, John Kappler (a professor of Immunology at National Jewish Health) and Brian Stadinski (Harvard Medical School) that peptides produced by such weak bonds are more likely to cause autoimmune disease. This carries clear implications beyond the diabetes field.

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

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