A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens.
Dendritic cells (DC) and other APCs rely on a number of specialized receptors to facilitate the uptake and intracellular accumulation of Ags. In this capacity, APCs use receptor-mediated endocytosis to enhance Ag presentation and the stimulation of Ag-specific T cells. Studies have demonstrated that the targeted delivery of Ags in vivo to CD91/the low-density lipoprotein receptor-related protein (CD91/LRP) induces enhanced activation of the adaptive immune system. However, the APC that mediates these augmented, Ag-specific responses remains to be characterized. In this study, we show that a subset of CD11c(+) lineage-negative (lin(-)) DC expresses the scavenger receptor CD91/LRP and that these rare APC are primarily responsible for the T cell activation that occurs following CD91/LRP-mediated Ag uptake in whole blood. The targeting of Ags to CD91/LRP results in enhanced receptor-mediated uptake within both lin(-) DCs and monocytes, and this uptake results in markedly increased T cell activation. Finally, purified cellular populations were used to demonstrate that CD11c(+) lin(-) DC, but not monocytes, are capable of stimulating T cell activation following CD91/LRP-mediated Ag uptake. Therefore, CD11c(+) lin(-) DC use CD91/LRP to facilitate the uptake and subsequent presentation of an array of Ags complexed within the CD91/LRP ligand, the activated form of alpha2-macroglobulin (alpha2M*).
Hart
Justin P
JP
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Gunn
Michael D
MD
Pizzo
Salvatore V
SV
D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism*; D039521:CD11c Antigen / Q000096:biosynthesis* / Q000097:blood; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D026563:LDL-Receptor Related Protein-Associated Protein / Q000096:biosynthesis / Q000502:physiology; D026502:LDL-Receptor Related Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D018110:Receptors, Lipoprotein; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D000511:alpha-Macroglobulins / Q000378:metabolism
D015703:Antigens, CD; D039521:CD11c Antigen; D026563:LDL-Receptor Related Protein-Associated Protein; D026502:LDL-Receptor Related Proteins; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018110:Receptors, Lipoprotein; D000511:alpha-Macroglobulins; C098773:low density lipoprotein receptor-related protein 8