The roles of membrane microdomains (rafts) in T cell activation

Detergent-resistant membrane microdomains enriched in sphingolipids, cholesterol and glycosylphosphatidylinositol-anchored proteins play essential roles in T cell receptor (TCR) signaling. These 'membrane rafts' accumulate several cytoplasmic lipid-modified molecules, including Src-family kinases, coreceptors CD4 and CD8 and transmembrane adapters LAT and PAG/Cbp, essential for either initiation or amplification of the signaling process, while most other abundant transmembrane proteins are excluded from these structures. TCRs in various T cell subpopulations may differ in their use of membrane rafts. Membrane rafts also seem to be involved in many other aspects of T cell biology, such as functioning of cytokine and chemokine receptors, adhesion molecules, antigen presentation, establishing cell polarity or interaction with important pathogens. Although the concept of membrane rafts explains several diverse biological phenomena, many basic issues, such as composition, size and heterogeneity, under native conditions, as well as the dynamics of their interactions with TCRs and other immunoreceptors, remain unclear, partially because of technical problems.