Lipid Rafts and T Cell Signalling

Plasma membrane microdomains, known as lipid rafts, have received a lot of attention over the last decade. It has become clear that the plasma membrane is far from homogenous, but many fundamental questions remain to be answered and the debate is still heated. It is suggested that lipid rafts result from the self-aggregation and tight packing of cholesterol and sphingolipids, forming domains with lower fluidity and a higher degree of saturation than the rest of the membrane. Lipid rafts should therefore be more ordered than the bulk membrane and are believed to exist in a liquid ordered state which resembles the liquid disordered state in that the lipids are fluid and the gel state in that the lipids are highly organised. Lipid rafts have been implicated in multiple cellular functions such as signalling, migration, exo- and endocytosis which has brought membrane studies to the foreground after decades in the shadow of protein and nucleic acid research. In T cells, lipid rafts are considered to be signalling hot spots enriched in molecules involved in signal transduction. Early T cell signalling events like tyrosine phosphorylation, phosphoinositide metabolism, ERK activation and calcium triggering can be activated by the aggregation of membrane microdomains enriched in the lipid raft marker GM1- a sphingolipid. We focus on the links between plasma membrane lipid rafts and the cytoskeleton as well as the importance of these links for T cell signalling thus directly addressing the function of lipid rafts in intact cells. We also investigate the relationships between temperature, lipid phases in the plasma membrane and T cell signalling. Extended knowledge on what makes a T cell commit to signalling is a key to understanding and interfering with the immune response. The project is multidisciplinary and involves biochemistry, molecular & cell biology, immunology as well as molecular modelling. It contains a great element of advanced fluorescence microscopy.