Transport of Streptococcus pneumoniae Capsular Polysaccharide in MHC Class II Tubules

PLoS Pathogens

Jens Rietdorf¹  David Schrama²  Jürgen C Becker²  Laura Groneck³  Mario Fabri³  Nirmal Robinson³  Wiltrud M Kalka-Moll³  Helena Hafke³  Martin Krönke³  Georg Plum³  Tom Li Stephen³  Harald Kropshofer⁴  Till A Röhn⁴ 

[1] Advanced Light Microscopy Facility, European Molecular Biology Laboratories, Heidelberg, Germany;Department of Dermatology, Julius-Maximilians-University of Wuerzburg, Wuerzburg, Germany;Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Cologne, Germany;Pharmaceutical Research, F. Hoffmann-La Roche AG, Basel, Switzerland

关键词: T cells;    Lysosomes;    Fluorescence imaging;    Abscesses;    Fluorescence microscopy;    Immune response;    Cell membranes;    Polysaccharides;   

DOI  :  10.1371/journal.ppat.0030032

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY