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OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway

Nature Immunology volume 1, pages 502–509 (2000)Cite this article

Abstract

We analyzed the interaction between a bacterial cell wall protein and dendritic cells (DCs). Outer membrane protein A from Klebsiella pneumoniae (kpOmpA) specifically bound to professional antigen presenting cells and was endocytosed by immature DCs via a receptor-dependent mechanism. kpOmpA signaled through Toll-like receptor 2, induced DCs to produce interleukin 12 and induced maturation of DCs. Whole antigen that was coupled to kpOmpA and injected into mice was taken up by DCs and delivered to the conventional cytosolic MHC class I presentation pathway. kpOmpA also primed antigen-specific CD8+ CTLs in the absence of CD4+ T cell help or adjuvant and elicited therapeutic immunity to antigen-expressing tumors. Thus, OmpA belongs to a class of proteins that are able to elicit CTL responses to exogenous antigen.

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Figure 1: kpOmpA binding and internalization by APCs.
Figure 2: Confocal microscopy analysis of kpOmpA localization.
Figure 3: TLR2 mediates cellular activation by OmpA.
Figure 4: Formation of Kb-SIINFKEL complexes after kpOmpA-OVA processing by DCs.
Figure 5: kpOmpA-OVA elicits CTLs and therapeutic tumor immunity.
Figure 6: kpOmpA-coupled melanoma associated antigens elicit specific CTL responses.

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Acknowledgements

We thank S. Amigorena (Institut Curie) for reviewing the manuscript and N. Shastri (University of California, CA) and L. Sherman (Scripps Institute and research foundation, La Jolla, CA) for providing the B3Z T cell hybridoma and the EL-4/A2Kb cells, respectively. We thank A. Blaecke, J. Challier and A. Gonzalez for technical assistance.

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  1. Toufic Renno, Liliane Goetsch, Isabelle Miconnet and Jean-Pierre Aubry: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre d'Immunologie Pierre Fabre, 5, Avenue Napoléon III, Saint-Julien en Genevois, F-74164, France

    Pascale Jeannin, Toufic Renno, Liliane Goetsch, Jean-Pierre Aubry, Yves Delneste, Nathalie Herbault, Thierry Baussant, Giovanni Magistrelli, Caroline Soulas & Jean-Yves Bonnefoy

  2. Ludwig Institute for Cancer research, Lausanne Branch, University of Lausanne, Epalinges, CH-1406, Switzerland

    Isabelle Miconnet, Pedro Romero & Jean-Charles Cerottini

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  1. Pascale Jeannin
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Correspondence to Pascale Jeannin.

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Jeannin, P., Renno, T., Goetsch, L. et al. OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway. Nat Immunol 1, 502–509 (2000). https://doi.org/10.1038/82751

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