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CD8⁺ Dendritic Cells Use LFA-1 to Capture MHC-Peptide Complexes from Exosomes In Vivo¹

Elodie Segura^*,, Coralie Guérin, Nancy Hogg, Sebastian Amigorena^*, and Clotilde Théry^2,*,

^* Centre de Recherche and Laboratoire de Cytométrie de Flux, Institut Curie, and Institut National de la Santé et de la Recherche Médicale, Unité 653, Paris, France; and Cancer Research United Kingdom, London Research Institute, London, United Kingdom

Exosomes are secreted vesicles formed in late endocytic compartments. Mature dendritic cells (DCs) secrete exosomes bearing functional MHC-peptide complexes and high levels of ICAM-1. Such exosomes can activate Ag-specific naive T cells but only after recapture by recipient APCs. In this study, we addressed the molecular mechanisms of interaction between exosomes and recipient DCs. We show that exosomes can be presented by mouse DCs without the need for internalization and processing. Exosomes interact with DCs through a specific saturable receptor. Although the two major ligands of ICAM-1, LFA-1 and Mac-1, are expressed by lymphoid organ DCs, only LFA-1 is required for exosome capture by these cells. Accordingly, we show that CD8⁺ DCs express higher levels of LFA-1 than CD8^– DCs, and that they are the main recipients of exosomes in vivo. We propose a new role for LFA-1 on DCs, as a receptor for exosomes to favor Ag transfer between DCs in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Ligue Nationale contre le Cancer, Institut National de la Santé et de la Recherche Médicale, Institut Curie, European Grant "DC for New Immunotherapies" 512074, and Cancer Research United Kingdom. E.S. was a fellow of Ministère de l’Education et de la Recherche.

² Address correspondence and reprint requests to Dr. Clotilde Théry, Institut Curie, Pavillon Pasteur, Institut National de la Santé et de la Recherche Médicale, Unité 653, 26 rue d’Ulm, 75005 Paris, France. E-mail address: clotilde.thery{at}curie.fr

³ Abbreviations used in this paper: DC, dendritic cell; WT, wild type.

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The JI 2007 179: 1411-1412. [Full Text]