Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II‐dependent pathway for antigen presentation

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Abstract
Summary: 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.