Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells
The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3+ (CD141+) subset DCs may be particularly effective in DC vaccination trials....
| প্রধান লেখক: | , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
American Society of Hematology
2012
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| _version_ | 1826291817290661888 |
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| author | Flinsenberg, T Compeer, E Koning, D Klein, M Amelung, F Van Baarle, D Boelens, J Boes, M |
| author_facet | Flinsenberg, T Compeer, E Koning, D Klein, M Amelung, F Van Baarle, D Boelens, J Boes, M |
| author_sort | Flinsenberg, T |
| collection | OXFORD |
| description | The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3+ (CD141+) subset DCs may be particularly effective in DC vaccination trials. BDCA-3+ DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3+ DCs in elicitation of HCMV-specific CD8+ T-cell clones. We show that Fcgamma-receptor (FcγR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3+ DCs. FcγR antigen targeting stimulates antigen uptake by BDCA-1+ rather than BDCA-3+ DCs. Conversely, BDCA-3+ DCs and not BDCA-1+ DCs show improved cross-presentation by FcγR targeting, as measured by induced release of IFNγ and TNF by antigen-specific CD8+ T cells. FcγR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcγRII is the most abundantly expressed FcγR on both BDCA-1+ and BDCA-3+ DCs. Furthermore we show that BDCA-3+ DCs express relatively more stimulatory FcγRIIa than inhibitory FcγRIIb in comparison with BDCA-1+ DCs. These studies support the exploration of FcγR antigen targeting to BDCA-3+ DCs for human vaccination purposes. |
| first_indexed | 2024-03-07T03:05:09Z |
| format | Journal article |
| id | oxford-uuid:b23e3c08-dda6-49f5-ae31-7acf28b7d7db |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:05:09Z |
| publishDate | 2012 |
| publisher | American Society of Hematology |
| record_format | dspace |
| spelling | oxford-uuid:b23e3c08-dda6-49f5-ae31-7acf28b7d7db2022-03-27T04:10:34ZFcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b23e3c08-dda6-49f5-ae31-7acf28b7d7dbEnglishSymplectic Elements at OxfordAmerican Society of Hematology2012Flinsenberg, TCompeer, EKoning, DKlein, MAmelung, FVan Baarle, DBoelens, JBoes, MThe reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3+ (CD141+) subset DCs may be particularly effective in DC vaccination trials. BDCA-3+ DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3+ DCs in elicitation of HCMV-specific CD8+ T-cell clones. We show that Fcgamma-receptor (FcγR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3+ DCs. FcγR antigen targeting stimulates antigen uptake by BDCA-1+ rather than BDCA-3+ DCs. Conversely, BDCA-3+ DCs and not BDCA-1+ DCs show improved cross-presentation by FcγR targeting, as measured by induced release of IFNγ and TNF by antigen-specific CD8+ T cells. FcγR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcγRII is the most abundantly expressed FcγR on both BDCA-1+ and BDCA-3+ DCs. Furthermore we show that BDCA-3+ DCs express relatively more stimulatory FcγRIIa than inhibitory FcγRIIb in comparison with BDCA-1+ DCs. These studies support the exploration of FcγR antigen targeting to BDCA-3+ DCs for human vaccination purposes. |
| spellingShingle | Flinsenberg, T Compeer, E Koning, D Klein, M Amelung, F Van Baarle, D Boelens, J Boes, M Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells |
| title | Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells |
| title_full | Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells |
| title_fullStr | Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells |
| title_full_unstemmed | Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells |
| title_short | Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells |
| title_sort | fcγ receptor antigen targeting potentiates cross presentation by human blood and lymphoid tissue bdca 3 dendritic cells |
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