Recently, Baud et al. demonstrated that mutation of Phe182 in EC2 abolished mOR-EG receptor activation supporting the importance of EC2 in ligand binding and receptor activation. The ligands identified in this study show significant structural diversity, suggesting plasticity within the ligand binding pocket and thus a broader molecular receptive range for MOR42-3 that had been previously suspected. A recent comprehensive study of MOR256-17 receptor using in vitro approach revealed that this particular receptor is able to detect odorants scattered across a large portion of odor space, confirming that it is broadly tuned. It favors multiple binding modes or conformations of the ligands within the binding pocket, which ultimately results in their broadly tuning. Olfactory receptors, like all GPCRs, exist in equilibrium of inactive and active states, which are likely reflected in conformational changes and rearrangements of helixes III, V, VI and VII during ligand binding and receptor activation. For example, the conserved NPxxY motif of the intracellular portion of helix VII undergoes marked backbone rearrangement during GPCR receptor activation and is present in MOR42-3 suggesting that similar activation process occurs within olfactory receptors. Pharmacological lipid lowering using statins is the primary medical therapy to reduce morbidity and mortality from atherosclerotic cardiovascular disease. This beneficial effect has been attributed to the plaque-stabilizing effects of cholesterol lowering accompanied by reduced inflammatory phenotype of atherosclerotic plaques as demonstrated both in clinical and preclinical studies. However, it is not known if the reduced inflammatory response is due to the direct effect of cholesterol lowering as demonstrated in preclinical studies or due to pleiotropic effects of statin. Cellular cholesterol plays a significant role in T cell responses. Increased accumulation of intracellular cholesterol content polarises T cells toward a more inflammatory phenotype ; whereas hypercholesterolemic milieu alters T helper response. It is known that cholesterol lowering by medication favorably affects the inflammatory response, but whether it affects T cell response remains unclear. Dietary modification to lower circulating cholesterol level is another effective strategy to modify atherosclerotic cardiovascular diseases. This benefit has been primarily attributed to its cholesterol lowering effect; however whether such cholesterol lowering affects T cell function also remains unknown. Previous studies have primarily studied the T cell response in lipid loading condition LY2109761 TGF-beta inhibitor comparing mice on high cholesterol chow vs. mice on normal chow. Change of T cell function has not been reported with cholesterol lowering after a period of hypercholesterolemia, a scenario similar to what occurs in clinical practice. Hence we conducted a series of in vitro and in vivo experiments to test the hypothesis that cholesterol lowering favorably modulates T cell function.