Peptide that triggers diabetes in mice identifiedJune 17th, 2010 - 12:43 pm ICT by ANI
Washington, June 17 (ANI): The precise protein fragment, or peptide, that can trigger diabetes in mice has been identified, thanks to researchers at National Jewish Health and the University of Colorado Anschutz Medical Campus.
The finding supports an emerging theory about the origins of autoimmunity, and may lead to new diagnostic and therapeutic strategies in humans.
“Our findings contradict conventional wisdom, which suggests that insulin peptides that are well presented to the immune system trigger diabetes. We believe, however, that the peptide we identified triggers diabetes precisely because it is so poorly presented to the immune system,” said Dr. John Kappler, Professor of Immunology at National Jewish Health.
The immune system tries to delete all T cells that might cause autoimmune disease.
During development in the thymus, immature T cells are exposed to “self” protein fragments, which are part of the organism.
T cells that recognize and bind to them are destroyed.
However, the above process is not foolproof, and autoimmune T cells do occasionally escape.
The development of type I diabetes in mice is associated with one form of MHCII, the molecule that holds and presents peptides to the immune system.
Previous research had identified a specific fragment of insulin, consisting of 12 linked amino acids, as the target of the autoimmune attack in type I diabetes.
The MHCII molecule, which has a binding pocket only 9 amino acids long, can bind to and present that insulin fragment in at least four different ways, known as registers.
Peptides bound in register present different subsets of amino acids to the T cells that cause diabetes.
Contrary to conventional wisdom, the research team found that the peptide presented in the register that binds most weakly to the MHCII molecule stimulated four different T cells associated with diabetes.
Peptides bound in the other registers did not stimulate those T cells.
“Although scientists have been closing in on the cause of type I diabetes, this is the first time that anyone has identified exactly what T cells recognize when they initiate an autoimmune attack in diabetes,” said co-author Dr. George Eisenbarth.
The findings support a theory recently posted by Kappler and colleagues at Harvard.
“This is the third time that a specific peptide and its binding register have been associated with autoimmune disease. All three have been peptides that are weakly bound to the MHCII molecule,” said Kappler.
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.
If the peptide is found to stimulate T cells associated with diabetes in humans, the discovery would suggest potential diagnostic and therapeutic strategies.
The study is published in the latest issue of the Proceedings of the National Academy of Sciences. (ANI)
- Researchers cure type 1 diabetes in mice - Apr 09, 2010
- Why some people with HIV develop AIDS and others don't - May 06, 2010
- How some people control HIV infection naturally - Nov 05, 2010
- Proteins' absence causes diabetes, rheumatoid arthritis - Sep 10, 2012
- Scientists illuminate cell pathway key to insulin resistance in type 2 diabetes - Feb 25, 2011
- Gene therapy may help cure diabetes - Jun 22, 2010
- Micro-RNA that regulates insulin in obesity identified - Apr 01, 2011
- Pair of liver molecules could control diabetes - Apr 09, 2012
- Fat, not sugar, contributes to Type-2 diabetes - Sep 04, 2012
- Brain insulin plays critical role in development of diabetes - Feb 17, 2011
- Eye colour linked to severity of skin conditions - May 07, 2012
- Missing sugar molecule 'increases diabetes risk' - Feb 25, 2011
- AIDS immunity is all in the proteins! - Dec 27, 2010
- Protein study sheds light on insulin response and cancer cell growth - Nov 06, 2010
- Vaccine to treat cat allergy developed - Apr 01, 2011
Tags: , , , , , , , , , , , , , , , , , , ,