Engineering an intracellular pathway for major histocompatibility complex class II presentation of antigens.
TC Wu, FG Guarnieri… - Proceedings of the …, 1995 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1995•National Acad Sciences
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 …
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 …
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.
National Acad Sciences