| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Unité d’Immunologie Clinique, Institut de la Santé et de la Recherche Médicale, Unité 255, Université Pierre et Marie Curie, Institut Curie, Paris, France;
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Laboratoire Mécanismes Moléculaires du Transport Intracellulaire, Institut Curie, Paris, France;
Institut Ludwig for Cancer Research, Brussels Branch, Brussels, Belgium;
§
Institut de la Santé et de la Recherche Médicale, Unité 520, Institut Curie, Paris, France; and
¶
Department of Biotechnology and Bioscience, University of Milan-Bicocca, Milan, Italy
Immunization with peptide or recombinant proteins generally fails to elicit CTL, which are thought to play a key role in the control of virus-infected cells and tumor growth. In this study we show that the nontoxic B subunit of Shiga toxin fused to a tumor peptide derived from the mouse mastocytoma P815 can induce specific CTL in mice without the use of adjuvant. The Shiga B subunit acts as a vector rather than as an adjuvant, because coinjection of the tumor peptide and the B subunit as separate entities does not lead to CTL induction. We also demonstrated that in vitro the B subunit mediates the delivery of various exogenous CD8 T cell epitopes into the conventional MHC class I-restricted pathway, as this process is inhibited by brefeldin A and lactacystin and requires a functional TAP system. In contrast to other nonviral methods for transport of exogenous Ags into the endogenous MHC class I pathway that involve macropinocytosis or phagocytosis, the Shiga B subunit targets this pathway in a receptor-dependent manner, namely via binding to the glycolipid Gb3. Because this receptor is highly expressed on various dendritic cells, it should allow preferential targeting of the Shiga B subunit to these professional APCs. Therefore, the Shiga B subunit appears to represent an attractive vector for vaccine development due to its ability to target dendritic cells and to induce specific CTL without the need for adjuvant.
This article has been cited by other articles:
|
|
 |
|
  O. Adotevi, B. Vingert, L. Freyburger, P. Shrikant, Y.-C. Lone, F. Quintin-Colonna, N. Haicheur, M. Amessou, A. Herbelin, P. Langlade-Demoyen, et al. B Subunit of Shiga Toxin-Based Vaccines Synergize with {alpha}-Galactosylceramide to Break Tolerance against Self Antigen and Elicit Antiviral Immunity J. Immunol., September 1, 2007; 179(5): 3371 - 3379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Luci, C. Hervouet, D. Rousseau, J. Holmgren, C. Czerkinsky, and F. Anjuere Dendritic Cell-Mediated Induction of Mucosal Cytotoxic Responses following Intravaginal Immunization with the Nontoxic B Subunit of Cholera Toxin. J. Immunol., March 1, 2006; 176(5): 2749 - 2757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schlecht, J. Loucka, H. Najar, P. Sebo, and C. Leclerc Antigen Targeting to CD11b Allows Efficient Presentation of CD4+ and CD8+ T Cell Epitopes and In Vivo Th1-Polarized T Cell Priming J. Immunol., November 15, 2004; 173(10): 6089 - 6097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Haicheur, F. Benchetrit, M. Amessou, C. Leclerc, T. Falguieres, C. Fayolle, E. Bismuth, W. H. Fridman, L. Johannes, and E. Tartour The B subunit of Shiga toxin coupled to full-size antigenic protein elicits humoral and cell-mediated immune responses associated with a Th1-dominant polarization Int. Immunol., October 1, 2003; 15(10): 1161 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Johannes The Epithelial Cell Cytoskeleton and Intracellular Trafficking: I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more Am J Physiol Gastrointest Liver Physiol, July 1, 2002; 283(1): G1 - G7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Smith, A. Gallimore, E. Jones, B. Roberts, J. M. Lord, E. Deeks, V. Cerundolo, and L. M. Roberts Exogenous Peptides Delivered by Ricin Require Processing by Signal Peptidase for Transporter Associated with Antigen Processing-Independent MHC Class I-Restricted Presentation J. Immunol., July 1, 2002; 169(1): 99 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Chikh, S. Kong, M. B. Bally, J.-C. Meunier, and M.-P. M. Schutze-Redelmeier Efficient Delivery of Antennapedia Homeodomain Fused to CTL Epitope with Liposomes into Dendritic Cells Results in the Activation of CD8+ T Cells J. Immunol., December 1, 2001; 167(11): 6462 - 6470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Cutler, R. Jotwani, and B. Pulendran Dendritic Cells: Immune Saviors or Achilles' Heel? Infect. Immun., August 1, 2001; 69(8): 4703 - 4708. [Full Text] [PDF]
|
|
|
|
|
|
O. Bruna-Romero and A. Rodriguez Dendritic Cells Can Initiate Protective Immune Responses against Malaria Infect. Immun., August 1, 2001; 69(8): 5173 - 5176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Falguieres, F. Mallard, C. Baron, D. Hanau, C. Lingwood, B. Goud, J. Salamero, and L. Johannes Targeting of Shiga Toxin B-Subunit to Retrograde Transport Route in Association with Detergent-resistant Membranes Mol. Biol. Cell, August 1, 2001; 12(8): 2453 - 2468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Etchart, P.-O. Desmoulins, K. Chemin, C. Maliszewski, B. Dubois, F. Wild, and D. Kaiserlian Dendritic Cells Recruitment and In Vivo Priming of CD8+ CTL Induced by a Single Topical or Transepithelial Immunization Via the Buccal Mucosa with Measles Virus Nucleoprotein J. Immunol., July 1, 2001; 167(1): 384 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lu, P. J. Wettstein, Y. Higashimoto, E. Appella, and E. Celis TAP-Independent Presentation of CTL Epitopes by Trojan Antigens J. Immunol., June 15, 2001; 166(12): 7063 - 7071. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
