HDL and adaptive immunity: A tale of lipid rafts

Abstract

Lipid rafts are membrane microdomains enriched with cholesterol, sphingolipids and proteins associated with several relevant biological processes, including signaling, protein transport, adhesion. The functional properties of lipid rafts are strictly depending upon their lipid composition; cholesterol depletion from these microdomains downregulates signaling pathways in several cells, including immune cells and disturb antigen-presenting ability [ [1] Anderson H.A. Hiltbold E.M. Roche P.A. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol. 2000; 1: 156-162 Crossref PubMed Scopus (298) Google Scholar ]. In fact, MHC class II molecules, that play a role in antigen presentation and signal transduction, localize in lipid-rich microdomains in antigen presenting cells (APCs) [ [2] Norata G.D. Pirillo A. Ammirati E. Catapano A.L. Emerging role of high density lipoproteins as a player in the immune system. Atherosclerosis. 2012; 220: 11-21 Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar ]. The number of MHC class II molecules present on the surface of APCs are crucial for the activation of T cells; lipid rafts concentrate MHC-peptide complex on APCs surface, decreasing the amount of antigen required for T cell activation [ [3] Zilber M.T. Setterblad N. Vasselon T. et al. MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes. Blood. 2005; 106: 3074-3081 Crossref PubMed Scopus (74) Google Scholar ]. HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by disrupting lipid rafts in antigen presenting cellsAtherosclerosisVol. 225Issue 1PreviewDepletion of cholesterol by methyl-β-cyclodextrin (MCD) on peptide-loaded antigen presenting cells (APCs) inhibits antigen presentation and T cell activation. However, whether membrane cholesterol efflux induced by high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) also results in inhibition of antigen presentation and T cell activation is still unknown. Full-Text PDF