A Newly Identified Antigen Retention Compartment in the FSDC Precursor Dendritic Cell Line
Abstract
Antigen uptake and presentation by dendritic cells (DC) occur at different stages of their maturation and are directed by certain cytokines (1–3). Phagocytosis (4) as well as mannose receptor-mediated endocytosis through clathrin-coated pits and fluid-phase macropinocytosis have been described for human and murine DC at the immature developmental stage (5, 6). Antigen presentation capacity of those cells is weak. After antigen contact with an atnigen or proinflammatory cytokines they mature under loss of the antigen uptake capabilities, but upregulate surface MHC class II and costimulatory molecules for antigen presentation. In vivo, resting DC of non-lymphoid organs internalize antigens and transport them to the draining lymph nodes. In the T cell areas of the lymph node the now fully mature interdigitating DC is able to initiate primary T cell responses. During migration the DC undergoes maturation, but antigen processing should be delayed until it reaches the lymph node. In the precursor DC line FSDC (6, 7), we have now identified a specialized antigen retention compartment, and propose a mechanism of how antigens within these vesicles are prevented from degradation by lysosomal enzymes.
Keywords
Dendritic Cell Mycobacterium Avium Lucifer Yellow Antigen Uptake Antigen Presentation CapacityPreview
Unable to display preview. Download preview PDF.
References
- 1.Steinman, R.M. 1991. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9: 271.CrossRefGoogle Scholar
- 2.Steinman, R.M., and J. Swanson. 1995. The endocytic activity of dendritic cells. J. Exp. Med. 182: 283.PubMedCrossRefGoogle Scholar
- 3.Lutz, M.B., G., Girolomoni, and P. Ricciardi-Castagnoli. 1996. The role of cytokines in functional regulation and differentiation of dendritic cells. Immunobiol. 195: 431.CrossRefGoogle Scholar
- 4.Reis e Souza, C., P.D. Stahl, and J.M. Austyn. 1993. Phagocytosis of antigens by Langerhans cells in vitro. J. Exp. Med. 178: 509.CrossRefGoogle Scholar
- 5.Sallusto, F., M. Cella, C. Danieli, and A. Lanzavecchia. 1995. dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class 11 compartment: down regulation by cytokines and bacterial products. J. Exp. Med. 182: 389.Google Scholar
- 6.Lutz, M.B., C.U. Aßmann, G. Girolomoni, and P. Ricciardi-Castagnoli. 1996. Different cytokines regulate antigen uptake and presentation of a precursor dendritic cell line. Eur J. Immunol. 26: 586.PubMedCrossRefGoogle Scholar
- 7.Girolomoni, G., Lutz, M.B., S. Pastore, C.U. Aßmann, and R. Ricciardi-Castagnoli. 1995. Establishment of a cell line with features of early dendritic cell precursors from mouse fetal skin. Eur. J. Immunol. 25: 2163.PubMedCrossRefGoogle Scholar
- 8.Demandolx, D. and J. Davoust. 1995. Multicolor analysis in confocal immunofluorescence microscopy. J. Trace Microprobe Tech. 13: 217.Google Scholar
- 9.Liou, W., H.J. Geuze, and A.J. Weerkamp. 1985. Localization of macromolecular components by application of the immunogold technique on cryosected bacteria. Methods Microbiol. 21: 211.Google Scholar
- 10.Anderson, R.G.W., J.R. Falk, J.L. Goldstein, and M.S. Brownl984. Visualization of acidic organelles in intact cells by electron microscopy. Proc. Natl. Acad. Sci USA 81: 4838.Google Scholar
- 11.Mellman, I., R. Fuchs, and A. Helenius. 1986. Acidification of the endocytic and exocytic pathways. Annu. Rev. immunol. 55: 663.Google Scholar
- 12.Rodriguez, G.M., and S. Diment. 1995. Destructive proteolysis by cysteine protease in antigen presentation of ovalbumin. Eur. J. Immunol. 25: 1823.PubMedCrossRefGoogle Scholar
- 13.Bohley, P., and P.O. Seglen. 1992. Protease and proteolysis in the lysosome. Experientia 48: 151.PubMedCrossRefGoogle Scholar
- 14.Crowle, A.J., R. Dahl, E. Ross, and M.H. May. 1991. Evidence that vesicles containing living, virulent Mycobacterium tuberculosis or Mycobacterium avium in cultured human macrophages are not acidic. Infect Immun. 59: 1823.Google Scholar
- 15.Pancholi, P., A. Mirza, N. Bhardwaj, and R.M. Steinman. 1993. Sequestration from immune CD4’ T cells of Mycobacteria growing in human macrophages. Science 260: 984.PubMedCrossRefGoogle Scholar
- 16.Kleijmeer, M.J., M.A. Ossevoort, C.J.H. van Veen, J.J. van Hellmond, J.J Neefjes, W.M. Kast, C.J.M. Me-lief, and H.J. Geuze. 1995. MHC class 11 compartment and the kinetics of antigen presentation in mouse spleen dendritic cells. J. Immunol. 154: 5715.PubMedGoogle Scholar