Delivery of lipids and liposomal proteins to the cytoplasm and Golgi of antigen-presenting cells

Liposomes have the well-known ability to channel protein and peptide antige ns into the MHC class II pathway of phagocytic antigen-presenting cells (AP Cs) and thereby enhance the induction of antibodies and antigen-specific T cell proliferative responses. Liposomes also serve as an efficient delivery system for entry of exogenous protein and peptide antigens into the MHC cl ass I pathway and thus are very efficient inducers of cytotoxic T cell resp onses. Soluble antigens that are rendered particulate by encapsulation in l iposomes are localized both in vacuoles and in the cytoplasm of bone marrow -derived macrophages. Utilizing fluorophore-labeled proteins encapsulated i n liposomes we have addressed the question of how liposomal antigens enter the MHC class I pathway. After phagocytosis of the liposomes, the fluoresce nt liposomal protein and liposomal lipids enter the cytoplasm where they ar e processed by the proteasome complex. The processed Liposomal protein is t hen transported via the TAP complex into the endoplasmic reticulum and the Golgi complex. Both the liposomal lipids and the liposomal proteins appear to follow the same intracellular route and they are processed as a protein- lipid unit. In the absence of a protein antigen (empty liposomes), there is no organelle-specific localization of the liposomal lipids. In contrast, w hen a protein is encapsulated in these liposomes, the distribution of the l iposomal lipids is dramatically affected and the liposomal lipids localize to the trans-Golgi area. Localization of the protein in the trans-Golgi are a requires liposomal lipids. Similarly, for the localization of liposomal l ipids in the trans-Golgi area, there is an obligatory requirement for prote in. Therefore, the intracellular trafficking patterns of Liposomal lipids a nd liposomal protein are reciprocally regulated. Presence of both liposomal lipids and liposomal protein in the trans-Golgi therefore facilitates the entry of Liposomal antigens into the MHC class I pathway. It is also possib le that liposomal lipids are presented to T cells via the recently describe d CD1 pathway for lipid antigens. Because liposome-formulated vaccines have the potential to stimulate antibody as well as cellular immune responses t o protein and lipid components, this approach could prove to be extremely u seful in designing vaccine strategies. Published by Elsevier Science B.V.