Lipid-based membrane microdomains in T cell activation

The immune system is able to mount an immune response against antigens present in the body at very low concentrations and, at the same time, to discriminate precisely between an infectious stimulus and a non-infectious one. During T cell activation, this sensitivity and specificity are achieved by mechanisms of sustained interactions with antigen-presenting cells (APC) as well as by tunable activation thresholds and signal modulation. Thus, in addition to the interaction between the T cell receptor (TCR) and its ligand, T cell activation depends on the combination of many other events involving costimulatory and inhibitory receptors, actin cytoskeleton and lipid membrane microdomains. Lipid rafts, shingolipid- and cholesterol-rich membrane microdomains, seem to be primarily involved in initiation and propagation of the signal transduction cascade associated to lymphocyte activation and might be used by T cells to fine-tune their immune responsiveness. In this article, we discuss recent results indicating that rafts are responsible for the spatial and temporal organization of the T cell signal transduction.