This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Basar, T.
Right arrow Articles by Leclerc, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Basar, T.
Right arrow Articles by Leclerc, C.

 Previous Article  |  Next Article 

Infection and Immunity, January 2000, p. 247-256, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Delivery of CD8+ T-Cell Epitopes into Major Histocompatibility Complex Class I Antigen Presentation Pathway by Bordetella pertussis Adenylate Cyclase: Delineation of Cell Invasive Structures and Permissive Insertion Sites

Radim Osicka,1 Adriana Osicková,1 Tümay Basar,1 Pierre Guermonprez,2 Marie Rojas,2 Claude Leclerc,2 and Peter Sebo1,*

Cellular and Molecular Microbiology Division, Institute of Microbiology of the Academy of Sciences of the Czech Republic, CZ-142 20 Prague 4, Czech Republic,1 and Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 75724 Paris, France2

Received 26 July 1999/Returned for modification 2 September 1999/Accepted 19 October 1999

Bordetella pertussis adenylate cyclase (AC) toxin-hemolysin (ACT-Hly) can penetrate a variety of eukaryotic cells. Recombinant AC toxoids have therefore been recently used for delivery of CD8+ T-cell epitopes into antigen-presenting cells in vivo and for induction of protective antiviral, as well as therapeutic antitumor cytotoxic T-cell responses. We have explored the carrier potential of the ACT molecule by insertional mutagenesis scanning for new permissive sites, at which integration of two- to nine-residue-long peptides does not interfere with membrane interaction and translocation of ACT. A model CD8+ T-cell epitope of ovalbumin was incorporated at 10 of these permissive sites along the toxin molecule, and the capacity of ACT constructs to penetrate into cell cytosol and deliver the epitope into the major histocompatibility complex (MHC) class I antigen processing and presentation pathway was examined. While all six constructs bearing the epitope within the Hly portion of ACT failed to deliver the epitope to the MHC class I molecules, all four toxoids with inserts within different permissive sites in the AC domain efficiently delivered the epitope into this cytosolic pathway, giving rise to stimulation of a specific CD8+ T-cell hybridoma. The results suggest that, in contrast to the AC domain, the hemolysin moiety of ACT does not reach the cytosolic entry of the MHC class I pathway.

* Corresponding author. Mailing address: Institute of Microbiology CAS, Vídenská 1083, CZ-142 20 Prague 4, Czech Republic. Phone: (4202) 475 2762. Fax: (4202) 472 2257. E-mail: sebo{at}biomed.cas.cz.

Infection and Immunity, January 2000, p. 247-256, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kamanova, J., Kofronova, O., Masin, J., Genth, H., Vojtova, J., Linhartova, I., Benada, O., Just, I., Sebo, P. (2008). Adenylate Cyclase Toxin Subverts Phagocyte Function by RhoA Inhibition and Unproductive Ruffling. J. Immunol. 181: 5587-5597 [Abstract] [Full Text]  
  • Fiser, R., Masin, J., Basler, M., Krusek, J., Spulakova, V., Konopasek, I., Sebo, P. (2007). Third Activity of Bordetella Adenylate Cyclase (AC) Toxin-Hemolysin: MEMBRANE TRANSLOCATION OF AC DOMAIN POLYPEPTIDE PROMOTES CALCIUM INFLUX INTO CD11b+ MONOCYTES INDEPENDENTLY OF THE CATALYTIC AND HEMOLYTIC ACTIVITIES. J. Biol. Chem. 282: 2808-2820 [Abstract] [Full Text]  
  • Bauche, C., Chenal, A., Knapp, O., Bodenreider, C., Benz, R., Chaffotte, A., Ladant, D. (2006). Structural and Functional Characterization of an Essential RTX Subdomain of Bordetella pertussis Adenylate Cyclase Toxin. J. Biol. Chem. 281: 16914-16926 [Abstract] [Full Text]  
  • Hervas-Stubbs, S., Majlessi, L., Simsova, M., Morova, J., Rojas, M.-J., Nouze, C., Brodin, P., Sebo, P., Leclerc, C. (2006). High Frequency of CD4+ T Cells Specific for the TB10.4 Protein Correlates with Protection against Mycobacterium tuberculosis Infection.. Infect. Immun. 74: 3396-3407 [Abstract] [Full Text]  
  • Majlessi, L., Simsova, M., Jarvis, Z., Brodin, P., Rojas, M.-J., Bauche, C., Nouze, C., Ladant, D., Cole, S. T., Sebo, P., Leclerc, C. (2006). An Increase in Antimycobacterial Th1-Cell Responses by Prime-Boost Protocols of Immunization Does Not Enhance Protection against Tuberculosis. Infect. Immun. 74: 2128-2137 [Abstract] [Full Text]  
  • Basler, M., Masin, J., Osicka, R., Sebo, P. (2006). Pore-Forming and Enzymatic Activities of Bordetella pertussis Adenylate Cyclase Toxin Synergize in Promoting Lysis of Monocytes. Infect. Immun. 74: 2207-2214 [Abstract] [Full Text]  
  • Tartz, S., Kamanova, J., Simsova, M., Sebo, P., Bolte, S., Heussler, V., Fleischer, B., Jacobs, T. (2006). Immunization with a Circumsporozoite Epitope Fused to Bordetella pertussis Adenylate Cyclase in Conjunction with Cytotoxic T-Lymphocyte-Associated Antigen 4 Blockade Confers Protection against Plasmodium berghei Liver-Stage Malaria. Infect. Immun. 74: 2277-2285 [Abstract] [Full Text]  
  • Wilkinson, K. A., Simsova, M., Scholvinck, E., Sebo, P., Leclerc, C., Vordermeier, H. M., Dickson, S. J., Brown, J. R., Davidson, R. N., Pasvol, G., Levin, M., Wilkinson, R. J. (2005). Efficient Ex Vivo Stimulation of Mycobacterium tuberculosis-Specific T Cells by Genetically Detoxified Bordetella pertussis Adenylate Cyclase Antigen Toxoids. Infect. Immun. 73: 2991-2998 [Abstract] [Full Text]  
  • Schlecht, G., Loucka, J., Najar, H., Sebo, P., Leclerc, C. (2004). Antigen Targeting to CD11b Allows Efficient Presentation of CD4+ and CD8+ T Cell Epitopes and In Vivo Th1-Polarized T Cell Priming. J. Immunol. 173: 6089-6097 [Abstract] [Full Text]  
  • Vordermeier, H. M., Simsova, M., Wilkinson, K. A., Wilkinson, R. J., Hewinson, R. G., Sebo, P., Leclerc, C. (2004). Recognition of Mycobacterial Antigens Delivered by Genetically Detoxified Bordetella pertussis Adenylate Cyclase by T Cells from Cattle with Bovine Tuberculosis. Infect. Immun. 72: 6255-6261 [Abstract] [Full Text]  
  • Martin, C., Requero, M.-A., Masin, J., Konopasek, I., Goni, F. M., Sebo, P., Ostolaza, H. (2004). Membrane Restructuring by Bordetella pertussis Adenylate Cyclase Toxin, a Member of the RTX Toxin Family. J. Bacteriol. 186: 3760-3765 [Abstract] [Full Text]  
  • El-Azami-El-Idrissi, M., Bauche, C., Loucka, J., Osicka, R., Sebo, P., Ladant, D., Leclerc, C. (2003). Interaction of Bordetella pertussis Adenylate Cyclase with CD11b/CD18: ROLE OF TOXIN ACYLATION AND IDENTIFICATION OF THE MAIN INTEGRIN INTERACTION DOMAIN. J. Biol. Chem. 278: 38514-38521 [Abstract] [Full Text]  
  • Loucka, J., Schlecht, G., Vodolanova, J., Leclerc, C., Sebo, P. (2002). Delivery of a MalE CD4+-T-Cell Epitope into the Major Histocompatibility Complex Class II Antigen Presentation Pathway by Bordetella pertussis Adenylate Cyclase. Infect. Immun. 70: 1002-1005 [Abstract] [Full Text]  
  • Fayolle, C., Osickova, A., Osicka, R., Henry, T., Rojas, M.-J., Saron, M.-F., Sebo, P., Leclerc, C. (2001). Delivery of Multiple Epitopes by Recombinant Detoxified Adenylate Cyclase of Bordetella pertussis Induces Protective Antiviral Immunity. J. Virol. 75: 7330-7338 [Abstract] [Full Text]  
  • Etchart, N., Desmoulins, P.-O., Chemin, K., Maliszewski, C., Dubois, B., Wild, F., Kaiserlian, D. (2001). 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. 167: 384-391 [Abstract] [Full Text]  
  • Lu, J., Wettstein, P. J., Higashimoto, Y., Appella, E., Celis, E. (2001). TAP-Independent Presentation of CTL Epitopes by Trojan Antigens. J. Immunol. 166: 7063-7071 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»