Bacterial capsular polysaccharides are virulence factors and are considered T cellindependent 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 IIdependent 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 celldependent 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 peptidecarbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens.