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. 1995 Dec 5;92(25):11671–11675. doi: 10.1073/pnas.92.25.11671

Engineering an intracellular pathway for major histocompatibility complex class II presentation of antigens.

T C Wu 1, F G Guarnieri 1, K F Staveley-O'Carroll 1, R P Viscidi 1, H I Levitsky 1, L Hedrick 1, K R Cho 1, J T August 1, D M Pardoll 1
PMCID: PMC40464  PMID: 8524826

Abstract

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-1 sorting signal reroutes the antigen into the MHC class II 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.

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