Intracellular processing of hapten-modified protein for MHC class I presentation: cytoplasmic delivery by pH-sensitive liposomes

Abstract

Phagocytic or endocytic uptake of pH-sensitive liposomes has been shown to result in the release of entrapped material into the cytosol. This system can therefore be applied to the targeted delivery of protein antigens into the MHC class I presentation pathway of antigen-processing cells. We have used trinitrophenyl (TNP)-modified chicken ovalbumin encapsulated in liposomes to examine the intracellular processing of haptenated proteins and the presentation of TNP-modified peptides to MHC class I-restricted hapten-specific CTL. Here, we demonstrate for the first time that hapten-modified proteins can undergo intracellular processing by macrophages, that similar peptides are produced in the form of unmodified or haptenated derivatives, and that TNP-peptides are transported to the cell surface and presented to class I-restricted CTL via the ER/Golgi pathway. This system can now be used to study T-cell responses to naturally processed hapten-conjugated peptides in vitro and in vivo.