Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination

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...

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Veröffentlicht in:The Journal of immunology (1950) 2015-03, Vol.194 (6), p.2696-2705
Hauptverfasser: Reuter, Anika, Panozza, Scott E, Macri, Christophe, Dumont, Claire, Li, Jessica, Liu, Haiyin, Segura, Elodie, Vega-Ramos, Javier, Gupta, Nishma, Caminschi, Irina, Villadangos, Jose A, Johnston, Angus P R, Mintern, Justine D
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container_end_page 2705
container_issue 6
container_start_page 2696
container_title The Journal of immunology (1950)
container_volume 194
creator Reuter, Anika
Panozza, Scott E
Macri, Christophe
Dumont, Claire
Li, Jessica
Liu, Haiyin
Segura, Elodie
Vega-Ramos, Javier
Gupta, Nishma
Caminschi, Irina
Villadangos, Jose A
Johnston, Angus P R
Mintern, Justine D
description 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.
doi_str_mv 10.4049/jimmunol.1402535
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subjects Animals
Antibodies - immunology
Antigen Presentation - immunology
Antigens, CD - immunology
Antigens, CD - metabolism
CD11b Antigen - immunology
CD11c Antigen - immunology
CD40 Antigens - immunology
Cells, Cultured
Dendritic Cells - immunology
Dendritic Cells - metabolism
Endocytosis - immunology
Histocompatibility Antigens Class I - immunology
Histocompatibility Antigens Class II - immunology
Humans
Immunology
Lectins, C-Type - immunology
Life Sciences
Mice, Inbred C57BL
Mice, Knockout
Minor Histocompatibility Antigens
Receptors, Cell Surface - immunology
Receptors, Immunologic - immunology
Vaccination - methods
Vaccines - administration & dosage
Vaccines - immunology
Vaccinology
title Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination
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