Reactive Nitrogen species process a microbial carbohydrate presented by the MHCII Pathway (93.20)

Abstract

Abstract The class II major histocompatibility complex (MHCII) pathway in antigen-presenting cells (APCs) is the conduit by which extracellular proteins are processed by proteases, resulting in foreign peptides being presented to T cells. After depolymerization to a markedly decreased molecular size, zwitterionic polysaccharides (ZPSs) are also presented by this pathway. However, nothing is known about the chemistry of carbohydrate processing apart from its dependence on the presence of inducible nitric oxide synthase (iNOS). By examining the ability of known nitric oxide-derived species, peroxynitrite, nitroxyl, and nitric oxide itself, to degrade polysaccharide A (PSA), a ZPS from Bacteroides fragilis, we determined that deamination was the predominant mechanism of PSA processing in APCs. Structural characterization of the nitric oxide-derived product PSA-NO indicated that the depolymerization didn¡t disturb PSA¡s repeat units with exception of the deamination cleavage of 4-amino groups of 3-linked 2-acetamido-4-amino-2,4,6-trideoxy galactopyranosyl (AATp) residues. PSA-NO presented by APCs induced CD4+ T cell proliferation that was blocked by inhibitors of endosomal processing and by an antibody to HLA-DR. A novel mechanism (deaminative reaction) differentiates carbohydrate from protein processing during the oxidative burst.