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

Anika Reuter, Scott E Panozza, Christophe Macri, Claire Dumont, Jessica Li, Haiyin Liu, Elodie Segura, Javier Vega-Ramos, Nishma Gupta, Irina Caminschi, Jose A Villadangos, Angus P R Johnston, Justine D Mintern

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38 Citations (Scopus)

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 CD82 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.
Original languageEnglish
Pages (from-to)2696-2705
Number of pages10
JournalJournal of Immunology
Volume194
Issue number6
DOIs
Publication statusPublished - 2015

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