Modulation of immunoproteasome subunits by liposomal lipid

Liposomes are phospholipid vesicles that have been used as carriers of antigens and adjuvants. Lipid A, the endotoxic moiety of Gram-negative bacterial lipopolysaccharicle is a potent adjuvant and incorporation into liposomes essentially reduces the endotoxic activity of lipid A. In this study, we analyzed the effect of liposomal lipid A [L(LA)] on the MHC class I antigen processing machinery in murine antigen presenting cells (APCs). L(LA) enhanced the surface expression of MHC class I, class II, CD80, and CD86 molecules, induced the secretion of IFN-gamma, IL-12p40, TNF-alpha and IL-10, and caused a shift in the proteasome profile from constitutive to immunoproteasomes as observed by the induction of beta 2i, beta 5i, PA28 alpha, and PA28 beta subunits. L(LA) acts through the production of IFN-gamma as demonstrated with APCs generated from IFN-gamma knockout mice. L(LA) therefore appears to act as an intracellular adjuvant by upregulating the antigen processing machinery, which could result in efficient antigen presentation. (c) 2008 Elsevier Ltd. All rights reserved.