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dc.contributor.authorLam, Jennifer S.en_US
dc.contributor.authorHuang, Haibinen_US
dc.contributor.authorLevitz, Stuart M.en_US
dc.date.accessioned2012-01-09T21:00:18Z
dc.date.available2012-01-09T21:00:18Z
dc.date.issued2007-10-10en_US
dc.identifier.citationLam, Jennifer S., Haibin Huang, Stuart M. Levitz. "Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells" PLoS ONE 2(10):e1009. (2007)en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/2144/2967
dc.description.abstractBACKGROUND. An experimental approach for improving vaccine efficacy involves targeting antigens to mannose receptors (MRs) on dendritic cells (DCs) and other professional antigen presenting cells. Previously, we demonstrated that mannosylated Pichia pastoris-derived recombinant proteins exhibited increased immunogenicity compared to proteins lacking mannosylation. In order to gain insight into the mechanisms responsible for this observation, the present study examined the cellular uptake of the mannosylated and deglycosylated recombinant proteins. METHODOLOGY/PRINCIPAL FINDINGS. Utilizing transfected cell lines, roles for the macrophage mannose receptor (MMR, CD206) and DC-SIGN (CD209) in the recognition of the mannosylated, but not deglycosylated, antigens were demonstrated. The uptake of mannosylated antigens into murine bone marrow-derived DCs (BMDCs) was inhibited by yeast mannans (YMs), suggesting a mannose-specific C-type lectin receptor-dependent process, while the uptake of deglycosylated antigens remained unaffected. In particular, antigens with both N-linked and extensive O-linked mannosylation showed the highest binding and uptake by BMDCs. Finally, confocal microscopy studies revealed that both mannosylated and deglycosylated P. pastoris-derived recombinant proteins localized in MHC class II+ compartments within BMDCs. CONCLUSIONS/SIGNIFICANCE. Taken together with our previous results, these data suggest that increased uptake by mannose-specific C-type lectin receptors is the major mechanism responsible for the enhanced antigenicity seen with mannosylated proteins. These findings have important implications for vaccine design and contribute to our understanding of how glycosylation affects the immune response to eukaryotic pathogens.en_US
dc.description.sponsorshipNational Institutes of Health (RO1 AI25780, RO1 AI37532)en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.titleEffect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cellsen_US
dc.typearticleen_US
dc.identifier.doi10.1371/journal.pone.0001009en_US
dc.identifier.pubmedid17925857en_US
dc.identifier.pmcid1995759en_US


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