Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Getting closer

01.07.2003


USC researchers have moved one step closer to understanding how the body fights harmful antigens – foreign molecules that trigger an immune response.

The team successfully simulated a mutation process that diversifies the proteins, or antibodies, responsible for immunity – a phenomenon known as somatic hypermutation. This process enables the body to fight off a wide range of diseases.

Their findings are detailed in the July 3 issue of the journal Nature.



"When performing laboratory – or in vitro experiments – you always hope to get results that are close to the real thing," said John Petruska, one of the paper’s authors and a professor of molecular biology in USC’s College of Letters, Arts & Sciences. "In this case, it is fascinating to discover that the somatic hypermutation process in vitro is nearly identical to that in a natural environment."

"This is the first step in building an in vitro system that would completely mimic the body’s immune response," Petruska added.

One of the first tactics the immune system uses to fight off foreign molecules is the production of protective antibody proteins, which are unique in their unlimited ability to diversify.

As one’s immune response intensifies, antibodies undergo mutations that enable them to attack foreign molecules more forcefully, said Phuong Pham, the paper’s lead author and a USC molecular biology postdoctoral researcher.

That process is known as somatic hypermutation.

Those more powerful antibodies allow the immune system to respond quickly and effectively to pathogens, particularly those from previous infections. In other words, the antibodies are much like soldiers sent to fight an enemy they’ve encountered in the past.

People whose immune systems lack the ability to create these strengthened antibodies may suffer from recurring bacterial and viral infections and do not respond to vaccinations.

Somatic hypermutation requires an enzyme called AID (Activation-Induced Cytidine Deaminase) which works on single-stranded DNA – a discovery made by the USC team earlier this year.

By allowing AID to work on single-stranded viral DNA containing a mutational marker gene, the researchers (using specialized laboratory techniques) were able to identify which DNAs contained mutations and which did not.

"The action of AID yielded the same specific mutational hot and cold spots along DNA strands that are observed in human antibody proteins," explained Myron F. Goodman, a professor of molecular biology and chemistry in USC’s College of Letters, Arts & Sciences and senior author of the Nature paper.

Those "hot" spots, identified by specific DNA sequences, allowed the researchers to clearly see where the mutations took place. In fact, the experiment yielded 14 out of 15 hot spots with perfect DNA sequences, demonstrating that the mutation process had gone off without a glitch.

"Remarkably, the results showed that AID acting alone on single-stranded DNA simulated the highly complex somatic hypermutation process that occurs in humans," Goodman said.

Furthermore, the team’s data revealed that the AID enzyme works its way along individual DNA strands, as opposed to jumping from one strand to another.

Because many of the DNA strands remained untouched as part of this methodical process, the team found that 98 percent of its experimental DNA had no mutations.

Among the 2 percent that did, half exhibited between one and 20 mutations, while the other half showed up to 80.

"It confirms that AID is working on individual pieces of DNA, instead of jumping around," Goodman said.

Overall, the USC team of researchers was impressed by AID’s role in the entire process.

"AID can’t account for somatic hypermutation by itself because we know that other enzymes are involved," Goodman explained. "But it’s pretty darn impressive to see that AID accounts for almost everything in the mutational targeting process."

The team’s work is yet another feat in the quest to uncover how the body’s immune system fights an enormous array of antigens, employing a delicate balance of mutations.

"Mutations can be both helpful and harmful," Petruska said. "Balance is key."

Gia Scafidi | EurekAlert!
Further information:
http://www.usc.edu/

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>