Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation

Abstract

The plasma membranes of eukaryotic cells are not uniform and possess distinct cholesterol- and sphingolipid-rich raft microdomains that are enriched in proteins known to be essential for cellular function. Lipid raft microdomains 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 antigen presentation has not been examined. MHC class II molecules were found to be constitutively present in plasma membrane lipid rafts in B cells. Disruption of these microdomains dramatically inhibited antigen presentation at limiting concentrations of antigen. The inhibitory effect of raft disruption on antigen presentation could be overcome by loading the APCs with exceptionally high doses of antigen, showing that raft association concentrates MHC class II molecules into microdomains that allow efficient antigen presentation at low ligand densities.

Receptor-mediated endocytosis of immune complexes in rat liver sinusoidal endothelial cells is mediated by FcγRIIb2

“…For example, rafts' association may concentrate a pool of the receptor at the cell surface that could facilitate antigen presentation to B cells, in a manner similar to raft-mediated increase in the cell surface density of MHC class II-peptide complexes to facilitate antigen presentation to T cells. 61 Taken together, these observations suggest that Fc␥RIIb2 in rat LSECs is used both in recycling and efficient IC clearance. These observations also lead us to consider an immunological role for Fc␥RIIb2, namely, antigen presentation to B cells.…”

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

“…In contrast to MHCII -Ii complexes, pMHCII is endocytosed via clathrin-and dynamin-independent pathway(s), possibly involving SWAP-70-regulated RhoA/ RhoB (Ocana-Morgner et al 2009) or Arf6-and Rab35-dependent mechanism(s) (Walseng et al 2008). MHCII is found in detergent-resistant membrane domains (DRMs) (Anderson et al 2000;Karacsonyi et al 2004;Rodgers and Smith 2005), and endocytosis of MHCII was severely hampered after treatment of cells with Filipin, a cholesterol-sequestering agent (Knorr et al 2009). Perhaps pMHCII uses the clathrinindependent carrier (GLIC)/GPI-AP-enriched early endosomal compartment (GEEC) pathway, an endocytosis route that is also used by lipid raft-associated molecules like GPI-linked proteins and cholera toxin B (Mayor and Pagano 2007;Howes et al 2010).…”

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

“…In DCs, lipid rafts are still poorly investigated. Recently, DC rafts have been shown to contain a subset of MHC class II-peptide complexes (24). Signals transmitted via DC rafts were shown to condition the DC for the activation of CD8 ϩ T cells (25).…”