Trafficking of liposomal antigen to the trans-Golgi of murine macrophages requires both liposomal lipid and liposomal protein

Major histocompatibility complex (MHC) class I molecules found on antigen-p resenting cells present peptides derived from cytoplasmic proteins to T cel ls. In contrast, peptides from exogenous proteins are mostly presented by c lass II molecules, It has been well established that liposomes can serve as an efficient delivery system for entry of exogenous protein antigens into the MHC class I pathway. Our previous studies utilizing fluorophore-labeled proteins encapsulated in liposomes demonstrated that after phagocytosis of the liposomes by bone marrow-derived macrophages (BMs), the processed pept ides were subsequently visualized in the trans-Golgi, while free conalbumin was excluded from the trans-Gels area, In the present study, we investigat ed whether liposomal lipids follow the same intracellular route as the lipo somal proteins after phagocytosis by BMs. Multilamellar liposomes with diff erent lipid compositions that also contained fluorescent phospholipids (emp ty liposomes) were incubated with murine BMs, Our results indicate that alt hough empty liposomes were avidly phagocytosed by macrophages, the fluoresc ent liposomal lipids did not localize to any particular area of the cell bu t were distributed throughout the cell, In contrast, when a protein was enc apsulated in the liposomes, the liposomal lipids were no longer dispersed t hroughout the cell, but were concentrated and localized in the trans-Golgi area. Furthermore, when the liposomes contained a fluorescent-labeled prote in, the fluorescent peptides also localized to the trans-Gels. These result s demonstrate that the combination of both liposomal lipids and liposomal p rotein is required for Golgi-specific targeting of liposomal antigens, Tran sport of both liposomal lipids and liposomal proteins to the Golgi complex, a major subcellular organelle in the passage of MHC class I molecules, mig ht explain why antigens encapsulated in liposomes readily induce cytotoxic T lymphocytes. (C) 1999 Academic Press.