title: Transport of Streptococcus pneumoniae capsular polysaccharide in MHC Class II tubules.
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.
authors: Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Cologne, Germany.
authors: Tom Li
authors: TL
authors: Stephen
authors: Mario
authors: M
authors: Fabri
authors: Laura
authors: L
authors: Groneck
authors: Till A
authors: TA
authors: Röhn
authors: Helena
authors: H
authors: Hafke
authors: Nirmal
authors: N
authors: Robinson
authors: Jens
authors: J
authors: Rietdorf
authors: David
authors: D
authors: Schrama
authors: Jürgen C
authors: JC
authors: Becker
authors: Georg
authors: G
authors: Plum
authors: Martin
authors: M
authors: Krönke
authors: Harald
authors: H
authors: Kropshofer
authors: Wiltrud M
authors: WM
authors: Kalka-Moll
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism; D016667:Bacterial Capsules / Q000378:metabolism*; D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D006681:HLA-D Antigens / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain