CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo.
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.
Segura
Elodie
E
Centre de Recherche, Institut Curie, Paris, France.
Guérin
Coralie
C
Hogg
Nancy
N
Amigorena
Sebastian
S
Théry
Clotilde
C
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism
D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments