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 |
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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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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1402535</identifier><identifier>PMID: 25653426</identifier><language>eng</language><publisher>United States: Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists</publisher><subject>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</subject><ispartof>The Journal of immunology (1950), 2015-03, Vol.194 (6), p.2696-2705</ispartof><rights>Copyright © 2015 by The American Association of Immunologists, Inc.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-502145c900e9904aaa35160a24f55c2afa784b417d443487b89ddac0d988f6f53</citedby><cites>FETCH-LOGICAL-c441t-502145c900e9904aaa35160a24f55c2afa784b417d443487b89ddac0d988f6f53</cites><orcidid>0000-0001-7511-1512</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25653426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02466412$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Reuter, Anika</creatorcontrib><creatorcontrib>Panozza, Scott E</creatorcontrib><creatorcontrib>Macri, Christophe</creatorcontrib><creatorcontrib>Dumont, Claire</creatorcontrib><creatorcontrib>Li, Jessica</creatorcontrib><creatorcontrib>Liu, Haiyin</creatorcontrib><creatorcontrib>Segura, Elodie</creatorcontrib><creatorcontrib>Vega-Ramos, Javier</creatorcontrib><creatorcontrib>Gupta, Nishma</creatorcontrib><creatorcontrib>Caminschi, Irina</creatorcontrib><creatorcontrib>Villadangos, Jose A</creatorcontrib><creatorcontrib>Johnston, Angus P R</creatorcontrib><creatorcontrib>Mintern, Justine D</creatorcontrib><title>Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><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.</description><subject>Animals</subject><subject>Antibodies - immunology</subject><subject>Antigen Presentation - immunology</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>CD11b Antigen - immunology</subject><subject>CD11c Antigen - immunology</subject><subject>CD40 Antigens - immunology</subject><subject>Cells, Cultured</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Endocytosis - immunology</subject><subject>Histocompatibility Antigens Class I - immunology</subject><subject>Histocompatibility Antigens Class II - immunology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Lectins, C-Type - immunology</subject><subject>Life Sciences</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Minor Histocompatibility Antigens</subject><subject>Receptors, Cell Surface - immunology</subject><subject>Receptors, Immunologic - immunology</subject><subject>Vaccination - methods</subject><subject>Vaccines - administration & dosage</subject><subject>Vaccines - immunology</subject><subject>Vaccinology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1rGzEQxUVpaByn95zKHtvDuiOtpN09GpPWAUMvzSUXMZZGjcJ-uJJs8H_fdW3nNMzj9x68x9gDh4UE2X5_C32_H8ZuwSUIVakPbMaVglJr0B_ZDECIkte6vmV3Kb0BgAYhP7FbobSqpNAz9rKKIVMMWPgxFo4GN_3BFpa6rohkaZcnPVFHNodx-E-R98EGGnKBQw7b0R3LjPEPZXLFAa0NA57Ye3bjsUv0-XLn7PnH4-_Vutz8-vm0Wm5KKyXPpQLBpbItALUtSESsFNeAQnqlrECPdSO3ktdOyko29bZpnUMLrm0ar72q5uzbOfcVO7OLocd4NCMGs15uzEmbOmstuTjwif16Zndx_LunlE0f0qkrDjTuk-ENNFrULdcTCmfUxjGlSP49m4M5rW-u65vL-pPlyyV9v-3JvRuuc1f_ALBcgiQ</recordid><startdate>20150315</startdate><enddate>20150315</enddate><creator>Reuter, Anika</creator><creator>Panozza, Scott E</creator><creator>Macri, Christophe</creator><creator>Dumont, Claire</creator><creator>Li, Jessica</creator><creator>Liu, Haiyin</creator><creator>Segura, Elodie</creator><creator>Vega-Ramos, Javier</creator><creator>Gupta, Nishma</creator><creator>Caminschi, Irina</creator><creator>Villadangos, Jose A</creator><creator>Johnston, Angus P R</creator><creator>Mintern, Justine D</creator><general>Publisher : Baltimore : Williams & Wilkins, c1950-. 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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.</abstract><cop>United States</cop><pub>Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists</pub><pmid>25653426</pmid><doi>10.4049/jimmunol.1402535</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7511-1512</orcidid><oa>free_for_read</oa></addata></record> |
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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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