Targeting antigen to MHC class II molecules promotes efficient cross-presentation and enhances immunotherapy

J Immunol. 2009 Feb 1;182(3):1260-9. doi: 10.4049/jimmunol.182.3.1260.

Abstract

An efficient pathway of cross-presentation common to a range of dendritic cell (DC) populations was identified by targeting Ag to MHC class II molecules. This finding was achieved by conjugating Ag to M1, which is a modified version of the superantigen streptococcal mitogenic exotoxin Z-2 that binds to MHC class II molecules but cannot directly stimulate T cells. M1 conjugates were efficiently presented to CD4(+) and CD8(+) T cells by bone marrow-derived DC and Langerhans cells in vitro. Whereas nonconjugated Ag was preferentially cross-presented by splenic CD8alpha(+) DC in vivo, M1-conjugated Ag was cross-presented by all dendritic subtypes assessed. Potent effector T cell responses with antitumor activity were elicited when M1 conjugates were injected together with an adjuvant. This method of Ag delivery has significant potential in therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Bacterial Toxins / administration & dosage*
  • Bacterial Toxins / immunology*
  • Bacterial Toxins / metabolism
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Cancer Vaccines / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Drug Delivery Systems / methods*
  • Exotoxins / administration & dosage*
  • Exotoxins / immunology*
  • Exotoxins / metabolism
  • Histocompatibility Antigens Class II / metabolism*
  • Ligands
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction / immunology
  • Superantigens / administration & dosage
  • Superantigens / immunology
  • Superantigens / metabolism

Substances

  • Bacterial Toxins
  • Cancer Vaccines
  • Exotoxins
  • Histocompatibility Antigens Class II
  • Ligands
  • Superantigens
  • mitogenic exotoxin Z protein, Streptococcus