Grant: Operating Grant

The goal of this study is to fully understand how cells of the immune system integrate signals to respond only when appropriate. Failure to tightly regulate this process results in needless damage to tissues and can lead to full-blown autoimmunity where the immune system mounts a sustained attack aimed at organs in the body. Our current focus is to study this process in human natural killer cells. These cells are part of the innate immune system and they are important in the body's defense against viruses and tumor development. Natural killer cells must distinguish normal healthy cells from a cell that has been infected by a virus or one that is malignant. Natural killer cells make this fateful decision using a collection of cell surface proteins that are called receptors, some of which send a positive signal that a cell is infected and some of which send inhibitory signals to indicate the cell is healthy. These receptors are called natural cytotoxicity receptors and killer cell inhibitory receptors respectively. We are using a combination of approaches to understand how the biochemical signals emanating from the receptors after engagement are integrated within the natural killer cell using a combination of cellular, biochemical and molecular techniques. We are also studying how genes encoding these receptors vary between people and how this variation impacts the immune response. The knowledge gained through these studies will help understand how these molecules contribute to the immune response and may be applied to the design of more effective vaccines for viral diseases and treatments for autoimmunity and cancer.