Concentration of MHC class II molecules in lipid rafts facilitates antigenpresentation

The plasma membranes of eukaryotic cells are not uniform and possess distin ct cholesterol- and sphingolipid-rich raft microdomains that are enriched i n proteins known to be essential for cellular function. Lipid raft microdom ains are important for T cell receptor (TCR)-mediated activation of T cells . However, the importance of lipid rafts on antigen presenting cells (APCs) and their role in major histocompatibility (MHC) class II-restricted antig en presentation has not been examined. MHC class II molecules were found to be constitutively present in plasma membrane lipid rafts in B cells. Disru ption of these microdomains dramatically inhibited antigen presentation at limiting concentrations of antigen. The inhibitory effect of raft disruptio n on antigen presentation could be overcome by loading the APCs with except ionally high doses of antigen, showing that raft association concentrates M HC class II molecules into microdomains that allow efficient antigen presen tation at low ligand densities.