The immune system is designed to rid the body of infections and unwanted cells, such as tumor cells or virally infected cells. The decision to target a certain agent for elimination is made by recognizing that a component (antigen) of a bacteria or virally infected cell is «foreign» to the body. Sometimes, however, the immune system can mistakenly target «self» components in healthy tissue, which leads to autoimmune diseases such as multiple sclerosis (MS). White blood cells called T cells are the central players in this decision making and are classically known to target protein components. Recently, however, it has been found that lipid components (ie. fats) can also be targeted by T cells, which is a new paradigm in immune recognition. We have been studying how T cells recognize lipids, and found that a major blood protein, apolipoprotein E (apoE), which was previously known to carry lipids for metabolic purposes, is also playing a role in the immune system to promote the recognition of lipids. ApoE has been known to play a role in many diseases, including MS and atherosclerosis (the disease of blood vessels which leads to heart disease and strokes). These two diseases also share common features in that there is immune system involvement which causes harm, in MS directed against the fatty insulation of nerves (myelin), and in atherosclerosis, immunity against unknown agents, possibly lipids found circulating in the blood. Our findings integrating lipid metabolism by apoE and the immune system thus open up a new area of research of direct relevance to MS and atherosclerosis, and we will set out to demonstrate that lipids are targeted in these diseases, and how apoE is involved to promote this mistaken targeting. Understanding these mechanisms will allow us to better monitor these disease using blood samples from patients, and also point to new strategies to treat disease by dampening or altering the immune response to lipids.