Effect of intrinsic and extrinsic lipids on T-cell signalling

Abstract

T-cell activation is dependent on activating and inhibitory signals and cell fate is influenced by the interplay between different these different signalling pathways. Because proximal events are relayed through the membrane via specific membrane microdomains called rafts, the lipid composition of the plasma membrane critically influences signal transduction and thus cellular functions. Rafts are highly motile domains, enriched in cholesterol compared to the rest of the membrane. Their specific lipid composition makes these domains very sensitive to external changes such as variations in the cholesterol, saturated and unsaturated fatty acid content of the immediate environment. Immune cells, and in particular T-cells, depend on membrane raft integrity for initiating signalling, so dysregulation of the processes involved in the maintenance of an adequate lipid environment is likely is to be a significant modulator of immune functions. In this chapter, we will review the modulation of TcR-dependent signalling events by lipids in in vitro and in vivo models focusing on the involvement of membrane rafts. Clinical cases such as autoimmune diseases, aging and Alzheimer's disease will be used to illustrate recent findings in this field.