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Mouse study could aid vaccine designers

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 mechani
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
27-May-2004


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