Transport of Streptococcus pneumoniae capsular polysaccharide in MHC Class II tubules.
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.
Stephen
Tom Li
TL
Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Cologne, Germany.
Fabri
Mario
M
Groneck
Laura
L
Röhn
Till A
TA
Hafke
Helena
H
Robinson
Nirmal
N
Rietdorf
Jens
J
Schrama
David
D
Becker
Jürgen C
JC
Plum
Georg
G
Krönke
Martin
M
Kropshofer
Harald
H
Kalka-Moll
Wiltrud M
WM
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*
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