title: Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II-dependent pathway for antigen presentation.
abstract: Some pathogenic bacteria form thick capsules that both block immune responses through inhibition of complement deposition and phagocytosis and stimulate a weak response resulting from a lack of T-cell involvement. Contrary to this model, capsular polysaccharides from 23 serotypes of Streptococcus pneumoniae have been successfully used in a multivalent vaccine in the absence of a carrier protein. Furthermore, type I pneumococcal polysaccharide (Sp1) has been shown to activate T cells in vivo and in vitro via an uncharacterized mechanism. In the present report, we demonstrate that Sp1 utilizes the major histocompatibility complex (MHC) class II pathway in antigen-presenting cells (APCs) for processing and presentation. APCs internalize and process Sp1 through a nitric oxide-dependent mechanism and, once inside the cell, it associates with MHC II proteins in an H-2M-dependent manner that leads to in vivo T-cell activation. These results establish that Sp1 activates T cells which can lead to abscess formation in mice through an H-2M-dependent polysaccharide antigen presentation pathway in APCs, potentially contributing to pneumococcal polysaccharide vaccine efficacy through the recruitment of T-cell help.
authors.affiliation: Department of Medicine, Channing Laboratory, Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Velez
authors.forename: Colleen J
authors.initials: CJ
authors.lastname: Lewis
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kasper
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D011992:Endosomes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000276:immunology*; D010084:Oxidation-Reduction; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000949:Histocompatibility Antigens Class II; D011135:Polysaccharides, Bacterial; C450843:pneumococcal polysaccharide type 1; D009569:Nitric Oxide
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