title: Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination.
abstract: Ab-targeted vaccination involves targeting a receptor of choice expressed by dendritic cells (DCs) with Ag-coupled Abs. Currently, there is little consensus as to which criteria determine receptor selection to ensure superior Ag presentation and immunity. In this study, we investigated parameters of DC receptor internalization and determined how they impact Ag presentation outcomes. First, using mixed bone marrow chimeras, we established that Ag-targeted, but not nontargeted, DCs are responsible for Ag presentation in settings of Ab-targeted vaccination in vivo. Next, we analyzed parameters of DEC205 (CD205), Clec9A, CD11c, CD11b, and CD40 endocytosis and obtained quantitative measurements of internalization speed, surface turnover, and delivered Ag load. Exploiting these parameters in MHC class I (MHC I) and MHC class II (MHC II) Ag presentation assays, we showed that receptor expression level, proportion of surface turnover, or speed of receptor internalization did not impact MHC I or MHC II Ag presentation efficiency. Furthermore, the Ag load delivered to DCs did not correlate with the efficiency of MHC I or MHC II Ag presentation. In contrast, targeting Ag to CD8(+) or CD8(-) DCs enhanced MHC I or MHC II Ag presentation, respectively. Therefore, receptor expression levels, speed of internalization, and/or the amount of Ag delivered can be excluded as major determinants that dictate Ag presentation efficiency in setting of Ab-targeted vaccination.
authors: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia; Max Planck Graduate Center, 55128 Mainz, Germany; Institute of Physical Chemistry, 55099 Mainz, Germany;
authors: Anika
authors: A
authors: Reuter
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia;
authors: Scott E
authors: SE
authors: Panozza
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia;
authors: Christophe
authors: C
authors: Macri
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia;
authors: Claire
authors: C
authors: Dumont
authors: Centre for Immunology, Burnet Institute, Melbourne, Victoria 3004, Australia;
authors: Jessica
authors: J
authors: Li
authors: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia;
authors: Haiyin
authors: H
authors: Liu
authors: INSERM Unité 932, 75248 Paris Cedex 05, France; Institut Curie, Centre de Recherche, 75248 Paris Cedex 05, France;
authors: Elodie
authors: E
authors: Segura
authors: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; and.
authors: Javier
authors: J
authors: Vega-Ramos
authors: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;
authors: Nishma
authors: N
authors: Gupta
authors: Centre for Immunology, Burnet Institute, Melbourne, Victoria 3004, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; and.
authors: Irina
authors: I
authors: Caminschi
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; and.
authors: Jose A
authors: JA
authors: Villadangos
authors: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Victoria 3052, Australia.
authors: Angus P R
authors: AP
authors: Johnston
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia; jmintern@unimelb.edu.au angus.johnston@monash.edu.
authors: Justine D
authors: JD
authors: Mintern
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D039481:CD11b Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; C529914:Clec9a protein, mouse; C093569:DEC-205 receptor; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014612:Vaccines