Specific cells of our body, termed immune cells, protect us from infection by pathogens. Immune cells themselves, however, must be kept under tight control, as pathological inflammation may otherwise occur. Additionally, autoimmunity may develop, as immune cells can potentially recognize normal components of our tissues. One of the mechanisms used to regulate the activity of immune cells is through expression of certain receptors on their cell membrane. When bound by a specific protein expressed by neighboring cells, these receptors transmit signals into the cell, resulting in the activation or silencing of the immune cell. We and others have shown that 3 subpopulations of immune cells, present in the liver, skin and intestine, express the regulatory receptor Ly49E. We have also shown that this Ly49E receptor is triggered by urokinase plasminogen activator, which is expressed during infection and in autoimmunity. We hypothesize that Ly49E expression has an important role during infection and in autoimmunity. To test this, we have generated a mouse strain that lacks expression of the Ly49E receptor. We will compare the immune response of the Ly49Edeficient mouse strain with that of ‘normal’ mice, and this in several models of infection and autoimmunity. These results will generate a better fundamental insight into the function of the Ly49E receptor and may lead to the development of biomedical tools that positively influence the immune response.