Open AccessEngineering an intracellular pathway for major histocompatibility complex class II presentation of antigens.
Author(s) -
T.C. Wu,
Frank Guarnieri,
Kevin F. Staveley-O’Carroll,
Raphael P. Viscidi,
Hyam I. Levitsky,
Lora Hedrick,
Kathleen R. Cho,
J. Thomas August,
Drew M. Pardoll
Publication year - 1995
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.25.11671
Subject(s) - antigen , biology , antigen presentation , major histocompatibility complex , mhc class i , antigen processing , cytotoxic t cell , virology , mhc class ii , cross presentation , mhc restriction , microbiology and biotechnology , immune system , immunology , t cell , in vitro , genetics
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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