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Stephen, TL; Fabri, M; Groneck, L; Rohn, TA; Hafke, H; Robinson, N; Rietdorf, J; Schrama, D; Becker, JC; Plum, G; Kronke, M; Kropshofer, H; Kalka-Moll, WM.
Transport of Streptococcus pneumoniae capsular polysaccharide in MHC class II tubules
PLOS PATHOG. 2007; 3(3):
Doi: 10.1371/journal.ppat.0030032
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- Co-authors Med Uni Graz
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Becker Jürgen Christian
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Schrama David
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- Abstract:
- Bacterial capsular polysaccharides are virulence factors and are considered T cell-independent antigens. However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+) T cells in a major histocompatibility complex (MHC) class II-dependent manner. The mechanism of carbohydrate presentation to CD4(+) T cells is unknown. We show in live murine dendritic cells (DCs) that Sp1 translocates from lysosomal compartments to the plasma membrane in MHCII-positive tubules. Sp1 cell surface presentation results in reduction of self-peptide presentation without alteration of the MHCII self peptide repertoire. In DM-deficient mice, retrograde transport of Sp1/MHCII complexes resulting in T cell-dependent immune responses to the polysaccharide in vitro and in vivo is significantly reduced. The results demonstrate the capacity of a bacterial capsular polysaccharide antigen to use DC tubules as a vehicle for its transport as an MHCII/saccharide complex to the cell surface for the induction of T cell activation. Furthermore, retrograde transport requires the functional role of DM in self peptide-carbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens.
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Animals -
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Antigen Presentation -
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Antigens, Bacterial - metabolism
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Antigens, Differentiation, B-Lymphocyte - metabolism
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Autoantigens - metabolism
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Bacterial Capsules - metabolism
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Biological Transport -
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CD4-Positive T-Lymphocytes - immunology
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Dendritic Cells - physiology
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Endosomes - metabolism
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HLA-D Antigens - physiology
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Histocompatibility Antigens Class II - metabolism Histocompatibility Antigens Class II - physiology
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Lymphocyte Activation -
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Mice -
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Mice, Inbred C57BL -
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Streptococcus pneumoniae - immunology