Atherosclerosis is the major cause of death in the western world, caused by an inflammatory process in the arteries. This inflammatory process involves both peptides as well as lipids in activation of T-cells. An immunologic response towards both oxLDL and native LDL has previously been identified. The existence of lipid antigens in atherosclerotic plaque is expected due to the occurrence of NKT cells in the plaque. 

I have here found both the source and a lipid antigen involved in the disease progression. Stimulated splenocytes with LDL and oxLDL in the presence or absence of LPS activates NKT cells with a secretion of IFNg, with an increased activation when co-stimulating the cells with LPS. Further investigations and purification of lipid components from LDL showed a specific fraction from LDL that stimulated iNKT cells only in the presence of LPS. Extracting human plaque with the same method gave iNKT cells activation with the same fraction and only when co-stimulated with LPS.  This fraction as been analyzed by mass spec and several cerebrosides and gangleosides was identified, among these beta-glucosylceramide was found. Commercial available beta-GlcCer was injected into ApoE ^-/- and ApoE^-/-CD1d^-/-  mice twice per week for 10 weeks. Treated mice had larger plaques in the aortic arch compared to control animals, this difference was not seen in ApoE^-/-CD1d^-/- mice proving that the effect was mediated by iNKT cells. Analyzes of the plaque in the aorta root showed an infiltration of CD4 cells and a higher number of MHC class II molecules in the plaque compered to control. These results shows that Beta-GlcCer is found in LDL and human atherosclerotic plaque, can activate NKT cells, but needs co-activation in in vitro stimulations and promote disease progression.