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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>