INTRACELLULAR PROCESSING OF HAPTEN-MODIFIED PROTEIN FOR MHC CLASS-I PRESENTATION - CYTOPLASMIC DELIVERY BY PH-SENSITIVE LIPOSOMES

Phagocytic or endocytic uptake of pH-sensitive liposomes has been show n to result in the release of entrapped material into the cytosol. Thi s system can therefore be applied to the targeted delivery of protein antigens into the MHC class I presentation pathway of antigen-processi ng 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 M HC class I-restricted hapten-specific CTL. Here, we demonstrate for th e first time that hapten-modified proteins can undergo intracellular p rocessing by macrophages, that similar peptides are produced in the fo rm of unmodified or haptenated derivatives, and that TNP-peptides are transported to the cell surface and presented to class I-restricted CT L via the ER/Golgi pathway. This system can now be used to study T-cel l responses to naturally processed hapten-conjugated peptides in vitro and in vivo.