ENGINEERING AN INTRACELLULAR PATHWAY FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II PRESENTATION OF ANTIGENS

The presentation of antigenic peptides by major histocompatibility complex (MHC) class II molecules to CD4(+) T cells is critical to the function of the immune system, In this study, we have utilized the sorting signal of the lysosomal-associated membrane protein LAMP-1 to target a model antigen, human papillomavirus 16 E7 (HPV-16 E7), into the endosomal and lysosomal compartments, The LAMP-I sorting signal reroutes the antigen into the MHC class ZI processing pathway, resulting in enhanced presentation to CD4(+) cells in vitro. In vivo immunization experiments in mice demonstrated that vaccinia containing the chimeric E7/LAMP-1 gene generated greater E7-specific lymphoproliferative activity, antibody titers, and cytotoxic T-lymphocyte activities than vaccinia containing the wild-type HPV-16 E7 gene, These results suggest that specific targeting of an antigen to the endosomal and lysosomal compartments enhances MHC class II presentation and vaccine potency.