Baccatin III, a synthetic precursor of taxol, enhances MHC-restricted antigen presentation in dendritic cells

Int Immunopharmacol. 2011 Aug;11(8):985-91. doi: 10.1016/j.intimp.2011.02.013. Epub 2011 Feb 24.

Abstract

Baccatin III, a precursor for the semisynthesis of taxol, is widely considered to be an inactive derivative of taxol. Here we show that baccatin III efficiently enhances MHC-restricted antigen presentation in dendritic cells. Baccatin III increased both class I- and class II-restricted presentation of exogenous OVA in bone marrow-derived dendritic cells (BM-DCs). Baccatin III also increased class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Baccatin III did not affect the phagocytic activity of BM-DCs. The antigen presentation-enhancing activity of baccatin III was examined further with nanoparticles containing OVA and baccatin III. Inclusion of baccatin III to nanoparticles containing OVA greatly enhanced their capacity to induce class I-restricted OVA peptide presentation in DCs both in vitro and in vivo. Accordingly, nanoparticles containing both OVA and baccatin III were much more efficient in inducing an OVA-specific CTL response in mice compared to those containing OVA only. These results demonstrate that baccatin III exerts immunomodulatory activities in vivo as well as in vitro on the MHC-restricted antigen presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / immunology
  • Alkaloids / pharmacology*
  • Animals
  • Antigen Presentation / drug effects*
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Immunologic Factors / immunology
  • Immunologic Factors / pharmacology
  • Lymphocyte Activation / drug effects
  • Major Histocompatibility Complex / drug effects*
  • Major Histocompatibility Complex / immunology
  • Mice
  • Nanoparticles
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Paclitaxel / immunology
  • Paclitaxel / pharmacology
  • T-Lymphocytes, Cytotoxic / drug effects
  • Taxoids / immunology
  • Taxoids / pharmacology*

Substances

  • Alkaloids
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunologic Factors
  • Taxoids
  • baccatin III
  • Ovalbumin
  • Paclitaxel