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

Tzyy Choou Wu, Frank G. Guarnieri, Kevin F. Staveley-O'Carroll, Raphael P. Viscidi, Hyam I. Levitsky, Lora Hedrick, Kathleen R. Cho, J. Thomas August, Drew M. Pardoll

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)11671-11675
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number25
DOIs
StatePublished - Dec 5 1995

Keywords

  • LAMP-1
  • human papillomavirus
  • recombinant vaccinia

ASJC Scopus subject areas

  • General

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