Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

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:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>