Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered ’branding’ process helps immune system cells pick their fights

18.05.2005


Finding may have ramifications for vaccines, autoimmunity and atherosclerosis



Scientists have uncovered a new method the immune system uses to label foreign invaders as targets to be attacked. Researchers showed that the immune system can brand foreign proteins by chemically modifying their structure, and that these modifications increased the chances that cells known as lymphocytes would recognize the trespassers and attack them. "Now that we know that some T cells need to see these types of modifications to identify an invader, we can see if incorporating such changes into the proteins is helpful for vaccination," says senior author Emil R. Unanue, M.D., the Edward Mallinckrodt Professor and head of Pathology and Immunology.

The finding may also be relevant to autoimmune conditions where the immune system erroneously attacks healthy tissues. Such disorders include rheumatoid arthritis, multiple sclerosis and type 1 diabetes. "We show in this study that during some infections, these same types of modifications can be made to our own proteins, potentially leading to T cell attacks on the self," says Unanue.


Unanue and colleagues, who publish their results on May 31 in the Proceedings of the National Academy of the Sciences, conducted their studies in mice and in cultures of mouse cells. Jeremy Herzog, a research associate in Unanue’s lab, did many of the experiments and was the lead author of the study.

T cells belong to a class of immune cells known as thymic-lymphocytes, which in turn are a component of the branch of the immune system known as adaptive immunity. This branch responds to pathogens after they interact with the other major branch, the innate immune system. T cells kill pathogens or produce molecules like cytokines that stop their growth. Scientists have known for some time that a second class of innate immune system cells known as antigen-presenting cells helps T cells determine what to attack. They do this by displaying fragments of proteins they have picked up on their surfaces for inspection by T cells. Fragments of proteins are called peptides.

Researchers also knew that when antigen-presenting cells are activated by inflammatory factors or microbial products, they start putting out chemically unstable compounds such as nitric oxide and superoxide. Together, these compounds generate peroynitrate, a highly potent chemical that modifies many proteins.

Unanue’s group showed that this chemical modifies the peptides presented by antigen-presenting cells in several distinct ways. For example, they attach a nitrate group to the amino acid tyrosine in the peptides, changing it to nitrotyrosine. Unanue’s lab then showed that these changes increased the chances that various types of T cells would react to the modified peptides shown to them by antigen-presenting cells.

Unanue’s group is working to substantiate their findings and explore their potential relevance to different areas of biomedical research. He notes that insulin-producing beta cells, the pancreatic cells attacked by T cells in type 1 diabetes, also generate reactive compounds similar to those made by antigen-presenting cells. "The beta cells could therefore be modifying their own proteins in the same way that antigen-presenting cells are modifying foreign proteins," he says. "We’re now investigating whether such modifications can cause T cells to attack the beta cells."

Damaging oxidative reactions are also believed to play a role in atherosclerosis. Scientists suspect oxidative damage in the blood vessel walls may lead to immune reactivity that contributes to narrowing and stiffening of blood vessels.

Herzog J, Maekawa Y, Cirrito TP, Illian BS, Unanue ER. Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells. Proceedings of the National Academy of the Sciences, 102 (22), 7928-7933.

Funding from the National Institutes of Health and the Kilo Diabetes and Vascular Research Foundation supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>