Elucidation of natural killer cell receptor function by genetic manipulation in the mouse

Natural killer (NK) cells are a type of white blood cell that is necessary for resistance to viral infection and cancer progression. NK cells protect the body by destroying cells, also known as target cells, that are virally infected or have become cancerous. This role is accomplished through proteins on the surface of NK cells specific for other proteins on the surface of target cells. Recently, a large family of NK cell receptors has been identified and have been termed 'Ly49'. There is some evidence that the Ly49 family of NK cell receptors are important in target cell recognition. We hope to show this by genetically engineering mice so that they do not express any Ly49 receptors on their NK cells. If Ly49 proteins are important for resistance to viruses and cancer, then these Ly49-deficient mice should be much more susceptible to such diseases. Understanding the mechanisms NK cells use to recognize target cells in the mouse will provide invaluable clues as to how human NK cells perform the same function. By understanding how NK cells help the body to fight off viruses and cancers, we will be better able to help those who are less resistant to these illnesses such as the very young, the very old and those who have compromised immune systems.