Intracellular trafficking of Fas ligand in cytotoxic T lymphocytes

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There is a type of white blood cell called a T cell that specializes in killing cancer cells or cells that have become infected with viruses or bacteria. This specialized T cell is called a cytotoxic T lymphocyte or CTL. CTL have two very effective ways of killing cells. The first way is the release of a number of proteins from the killer cell, called cytolytic molecules, which are able to enter the defective cell and kill it. The other mechanism is the expression of a molecule on the cell surface called Fas ligand (FasL) that triggers cells that have a molecule called Fas on the cell surface to commit suicide. Since essentially all cells in the body have Fas on the cell surface, the CTL must tightly control the amount of FasL on the cell surface so that they do not go around and trigger all of the cells in the body to commit suicide. We have found that CTL control the amount of FasL on the cell surface by holding the FasL in vesicles, or bags, within the cell. When the CTL recognizes that a cell is abnormal in some way, it then quickly moves the FasL to the cell surface but only in the direction where the normal cell is bound, where it triggers suicide of the cell, and then the FasL rapidly disappears again from the cell surface. This is an effective way to kill only the infected cell while sparing the normal surrounding cells. This study is focused on trying to understand how the FasL is stored in these vesicles in the cell and what triggers it to move to the cell surface. We will use a sophisticated microscope to visualize the movement of FasL in CTL in real time when it encounters an abnormal cell. This will allow us to determine the conditions that cause the movement and deployment of the FasL to the cell surface. We will also gain insight into how cells can control the movement and directional localization of molecules.