Targeting of antigen via XCR1, the lineage marker for cross-presenting dendritic cells, elicits potent CD8 cytotoxicity in vivo

Abstract

Event Abstract Back to Event Targeting of antigen via XCR1, the lineage marker for cross-presenting dendritic cells, elicits potent CD8 cytotoxicity in vivo Evelyn Hartung1, Martina Becker1, Annabell Bachem1, Nele Reeg1, Yi Yang1, Anika Jäkel1, Harald Weber1, Volker Henn1, Hans-Werner Mages1 and Richard A. Kroczek1* 1 Robert Koch Institute, Molecular Immunology, Germany Current vaccines essentially elicit protective neutralizing antibodies. However, some pathogens like mycobacteria, hepatitis C virus, Plasmodium, or HIV can only be cleared by cytotoxic T cells. We have recently shown that the chemokine receptor XCR1 is selectively expressed on cross-presenting dendritic cells (DCs), the key players in the induction of CD8+ T cell cytotoxicity. Based on this finding we have now established model systems for antigen targeting into cross-presenting DCs via XCR1. To this end, a mAb to murine XCR1 (MARX10) or XCL1, the natural chemokine ligand for XCR1, were fused to ovalbumin using recombinant techniques. Neither targeting reagent activated DCs when injected without adjuvant. A single i.v. injection of small amounts (1 2.5 µg) of either targeting reagent, applied together with LPS, efficiently induced proliferation and expansion of antigen-specific CD4+ and CD8+ T cells. Both targeting systems generated potent CD8+ T cell killing capacity in naïve C57BL/6 mice, when tested using an in vivo kill assay and an aggressive tumor model system. Both targeting strategies were highly specific as neither proliferation nor cytotoxicity was detected in XCR1-deficient mice. In clear contrast, injection of soluble ovalbumin was ineffective in all assay systems used. We thus could demonstrate that targeting of antigen into murine cross-presenting DCs via XCR1 induces a potent antigen-specific cytotoxic CD8+ T cell response in vivo. Since XCR1 is also selectively expressed on human cross-presenting CD141+ DCs, these targeting strategies will be transferable to the human, enabling the development of novel preventive and therapeutic vaccines. Keywords: targeting, cross-presentation, Dendritic Cells, Cytotoxicity, Vaccination, XCR1, XCL1 Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Hartung E, Becker M, Bachem A, Reeg N, Yang Y, Jäkel A, Weber H, Henn V, Mages H and Kroczek RA (2013). Targeting of antigen via XCR1, the lineage marker for cross-presenting dendritic cells, elicits potent CD8 cytotoxicity in vivo. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00937 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Richard A Kroczek, Robert Koch Institute, Molecular Immunology, Berlin, Germany, KroczekR@rki.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Evelyn Hartung Martina Becker Annabell Bachem Nele Reeg Yi Yang Anika Jäkel Harald Weber Volker Henn Hans-Werner Mages Richard A Kroczek Google Evelyn Hartung Martina Becker Annabell Bachem Nele Reeg Yi Yang Anika Jäkel Harald Weber Volker Henn Hans-Werner Mages Richard A Kroczek Google Scholar Evelyn Hartung Martina Becker Annabell Bachem Nele Reeg Yi Yang Anika Jäkel Harald Weber Volker Henn Hans-Werner Mages Richard A Kroczek PubMed Evelyn Hartung Martina Becker Annabell Bachem Nele Reeg Yi Yang Anika Jäkel Harald Weber Volker Henn Hans-Werner Mages Richard A Kroczek Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.