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Targeted delivery of mycobacterial antigens to human dendritic cells via Siglec-7 induces robust T cell activation

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  • Lipids from mycobacteria can be presented to human T cells by group 1 CD1 Ag-presenting molecules (CD1a, CD1b, and CD1c). Group 1 CD1-restricted T cells are activated by lipid Ags presented by myeloid dendritic cells (DCs), after which they generate antibacterial effector functions, including IFN-γ secretion and cytolysis. Thus, mycobacterial lipids are being investigated as components of novel vaccines for mycobacterial infections. In this study we show that the mycobacterial lipid Ag C80 glucose-6-monomycolate can be delivered to human CD1b+ DCs via targeted liposomal nanoparticles, leading to robust group 1 CD1-restricted activation of T cells. Targeting was achieved by decorating the liposomes with a high-affinity glycan ligand of sialic acid–binding Ig-like lectin (Siglec)-7, a siglec receptor expressed on DCs that mediates rapid endocytosis and transport of its cargo to lysosomes. An Ab to Siglec-7 completely blocked the binding of targeted liposomes to human monocyte-derived DCs (Mo-DCs), demonstrating their targeting specificity. Mo-DCs pulsed with targeted liposomes containing C80 glucose-6-monomycolate more potently activated a CD1b-restricted T cell line relative to Mo-DCs pulsed with free lipid Ag or antigenic liposomes without Siglec-7 ligand. These data suggest that the endocytic function of Siglec-7 can be exploited to deliver glycolipid Ags to their target cell and increase the efficiency of display to T cells.

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    © 2014 N. Kawasaki et al. This version of this article is open access and can be downloaded and shared. The original author(s) and source must be cited.
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    • Kawasaki, N., Rillahan, C. D., Cheng, T. Y., Van Rhijn, I., Macauley, M. S., Moody, D. B., & Paulson, J. C. (2014). Targeted delivery of mycobacterial antigens to human dendritic cells via Siglec-7 induces robust T cell activation. The Journal of Immunology, 193(4), 1560-1566.
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