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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