(Philadelphia, PA) In a way, the immune system works like throwing a fistful of darts while blindfolded if you throw enough some may actually hit the dartboard. Since the immune system does not know ahead of time what a particular threat looks like, it generates T cells, a type of white blood cell, with uniquely random T cell receptors (TCRs). Once the TCR gets activated by latching onto a target it begins a cascade of signals and counter-signals that work in order to prepare the T cell for action. In this weeks issue of the journal, Science, researchers from the University of Pennsylvania School of Medicine report their findings on the role of one signal, the SLAP-130 protein, in bridging together chemical pathways in order to activate T cells.

"Once the immune system finds the TCR that sticks to a specific target, it generates more copies of that T cell and readies them to seek out the target a process that is regulated by an intricate network of chemical reactions," said Gary A. Koretzky, PhD, professor in the Penn Department of Pathology and Laboratory Medicine, and researcher for the Abramson Family Cancer Research Institute at the Penn Cancer Center. "Part of our goal is to figure out which signal does what in this activation process."

According to Koretzky, the SLAP-130 protein is an integral part of generating an immune response. Using a mouse model, Koretzky and his colleages were able to place SLAP-130 in the chain of reactions that couple TCR activation with the activation of integrins, large molecules on the outside of T cells that help them stick to their targets. Without SLAP-130 to link the two processes together, T cells are not able to get the integrins to work properly.

"By identifying how T cells are activated, we hope to gain a better understanding of how T ce
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Contact: Greg Lester
lesterg@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
21-Sep-2001