Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery Prompts New Theory on Cause of Diabetes, Other Autoimmune Diseases

03.05.2010
The recent discovery of a protein fragment capable of causing diabetes in mice has spurred researchers at National Jewish Health and the University of Colorado Denver to propose a new hypothesis about the cause of diabetes and autoimmunity in general.

In the April 23, 2010, issue of Immunity, Drs. Brian Stadinski, John Kappler and George Eisenbarth propose that the unusual and rare presentation of protein fragments (peptides) to the immune system allows autoreactive T cells to escape the thymus and trigger autoimmune disease (abstract). The findings could lead to a new strategy for preventing type 1 diabetes.

"The immune system normally deletes dangerous, autoreactive T cells that recognize ‘self" peptides, which are a normal part of the organism," said Dr. Kappler, Professor of Immunology at National Jewish Health. "We believe autoreactive T cells in diabetes and other autoimmune diseases escape destruction in the thymus because they never see these poorly presented peptides there. But the T cells do encounter those peptides elsewhere in the body and trigger an autoimmune attack."

Autoimmune diseases, such as type 1 diabetes, multiple sclerosis and lupus, occur when the immune system turns against its own body. This attack is often led by T cells, which serve as coordinators and effectors of the adaptive immune response. During development the immune system tries to protect against this by subjecting T cells to a stringent selection process in the thymus. Any T cell with receptors that bind to self proteins are destroyed before they can circulate throughout the body. This system does occasionally fail, however, opening the door to autoimmune disease.

It has been a challenge for scientists to identify which peptides the autoreactive T cells bind to when they initiate autoimmune disease. Drs. Kappler, Stadinski and Kathryn Haskins, however, recently reported in Nature Immunology (abstract) that they had identified a small piece of the protein chromogranin A as the target for one of the most pathogenic T cells in a mouse model of diabetes. This, in conjunction with other discoveries, led them to a new hypothesis about diabetes and autoimmunity.

Cells display protein fragments, or peptides, on their surfaces. The peptides can be derived from self proteins or infectious organisms. The cells hold these peptides with a special protein, known as MHC in mice, sort of like a hotdog bun (MHC) holding a hotdog (peptide). If a T cell, with its unique receptor, can bind to the combined MHC-peptide pair, it is activated and initiates an immune response against that peptide or cells displaying it.

In the case of the chromogranin A peptide, the researchers found that it binds to MHC in an odd way. Instead of fitting cleanly in the MHC binding groove, it fills only part of the groove, hanging over the side and binding to a different area, much like a foot-long hotdog hanging out one end of a normal-sized bun. The peptide also binds very weakly to the MHC molecule.

Another team of researchers found a similar situation with an animal model of multiple sclerosis; only part of the MHC binding groove is filled and the peptide binds only weakly to MHC. Dr. Kappler and his colleagues suspect that a similar situation may occur in diabetes with a peptide from the insulin protein.

Drs. Kappler, Stadinski and Eisenbarth believe these autoimmune antigens may be important precisely because they bind so oddly and weakly to the MHC molecule. The researchers propose that such unusual binding means that these particular MHC-peptide pairs show up only rarely, or never, in the thymus where T-cell selection occurs. Out in the rest of the body, however, specialized processing of the proteins or high concentrations of the source protein produce enough of those odd MHC-protein complexes for the T cells to find them.

"When these T cells encounter the self protein for the first time in the periphery, they initiate an autoimmune response," said Dr. Kappler.

Diabetes and other autoimmune diseases have been associated with specific, relatively rare forms of MHC molecules. Kappler and his colleagues believe these rare forms of MHC are part of the autoimmune puzzle.

"Other scientists have proposed that the MHC molecules associated with autoimmune diseases bind all peptides weakly," said Dr. Kappler. "We think, however, that the MHC molecules can bind peptides perfectly well, but that their unique shape allows them to weakly bind and present peptides that no other MHC molecules can."

William Allstetter | EurekAlert!
Further information:
http://www.njhealth.org

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>