Cytotoxic T lymphocytes induced by liposomal antigens: mechanisms of immunological presentation.

It is known that liposomes can deliver encapsulated substances, including drugs and antigens, to lysosomes in macrophages. Because of this it has been assumed that although liposomes might be useful for induction of humoral (class II) immunity, they would not be capable of cytoplasmic delivery of antigen for introduction into the class I pathway leading to induction of cytotoxic T lymphocytes (CTLs). However, experiments conducted by numerous laboratories, including our own, have demonstrated the ability to induce CTLs either in vitro with cultured cells incubated with liposome-associated antigen, or in vivo after immunization of mice or monkeys with liposomes containing associated antigen. Using a monoclonal antibody that recognizes repeating sequences of tetrapeptide epitopes derived from the circumsporozoite protein of Plasmodium falciparum, it has been shown by immunogold electron microscopy that liposomal antigenic epitopes can actually spill from endosomes into the cytoplasm of cultured macrophages. On the basis of this observation, a theoretical intracellular pathway is proposed whereby liposomal antigen is processed by macrophages through a cytoplasmic process that results in delivery of antigenic epitopes to the Golgi apparatus and the endoplasmic reticulum. The liposomal antigenic epitopes would then have the opportunity to associate with class I MHC molecules and undergo vesicular transport to the surface of the cells for presentation and induction of CTLs.