Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse study could aid vaccine designers

28.05.2004


Investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have conducted studies in mice to gain a new picture of how the immune system’s "killer" T cells are prompted to destroy infected cells. Their insights provide a blueprint for rational design of vaccines that induce desired T-cell responses.



The findings are published in this week’s Science. "If we are correct, what we’ve found will put rational vaccine design on a firmer footing," says Jonathan Yewdell, M.D., Ph.D., who led the NIAID team.

T cells belong to the cellular arm of the immune system’s two-pronged defense mechanism against foreign invaders--the other arm features blood-borne antibodies. Historically, vaccines aimed to stimulate antibody production in a bid to prevent specific diseases. More recently, scientists have begun to manipulate T cells to create vaccines effective against pathogens that antibodies alone cannot control. Such T-cell-inducing vaccines are being tested against infectious diseases such as HIV/AIDS and hepatitis and are being studied as treatments for certain cancers.


Once alerted to the presence of infected cells, resting T cells are "awakened" and begin to multiply rapidly. Then they zero in on and destroy infected cells while sparing uninfected ones. Rousing slumbering T cells is the job of dendritic cells, the sentinels of the immune system. Dendritic cells activate the T cells by displaying peptides--small pieces of virus or other foreign protein--on their surfaces. In a process called direct priming, dendritic cells generate these peptides by themselves after being infected by a virus. Alternatively, dendritic cells may first interact with other body cells that have been infected by a virus and then activate the T cells. This indirect route is called cross-priming.

Vaccines may exploit either route to T-cell priming, but scientists have not known enough about the mechanisms behind cross-priming to exploit this route in vaccine design.

Test tube experiments suggested that molecular "chaperones" accompany peptides from infected cells to dendritic cells, and a number of experimental vaccines have been designed on this premise. But few studies have been done to determine if chaperoned peptides play any role in animal systems, notes Dr. Yewdell.

If the chaperoned peptide theory is correct, infected cells that make the most peptides should most strongly stimulate cross-priming. Conversely, fewer peptides should mean less cross-priming. To test this prediction, Dr. Yewdell and his colleagues created virus-infected cells that were genetically or chemically prevented from producing peptides and injected those cells into mice. They found the opposite of what they expected: cross-priming correlated directly with levels of whole proteins, rather than levels of peptides, expressed by the virus-infected cells.

This new information could aid vaccine design, says Dr. Yewdell. "Our experiments indicate that two distinct pathways exist to prime T cells," he says. If the rules for T-cell priming suggested by these experiments are correct, vaccines meant to interact with dendritic cells should be designed to generate large amounts of peptides, while vaccines that target other kinds of cells should be designed to generate whole proteins that will go on to be processed in the dendritic cells during T-cell cross-priming.

Prompting a strong and specific T-cell reaction may be the key to vaccines that are effective against certain infectious diseases, including HIV/AIDS and malaria, notes Dr. Yewdell. It is also possible that a therapeutic vaccine might be developed to boost the T cell activity of people who have chronic liver infections caused by hepatitis B or C viruses.


NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.

Reference: CC Norbury et al. CD8+ cell cross-priming via transfer of proteasome substrates. Science 304:1318-21 (2004).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Anne A. Oplinger | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>