Abstract:
:After uptake by the endosome of an antigen-presenting cell (APC), exogenous proteins are known to be degraded into peptides by protease digestion. Here, we report the mechanism by which pure carbohydrates can be depolymerized within APC endosomes/lysosomes by nitric oxide (NO)-derived reactive nitrogen species (RNSs) and/or superoxide-derived reactive oxygen species (ROSs). Earlier studies showed that depolymerization of polysaccharide A (PSA) from Bacteroides fragilis in the endosome depends on the APC's having an intact inducible nitric oxide synthase (iNOS) gene; the chemical mechanism underlying depolymerization of a carbohydrate within the endosome/lysosome is described here. Examining the ability of the major RNSs to degrade PSA, we determined that deamination is the predominant mechanism for PSA processing in APCs and is a required step in PSA presentation to CD4(+) T cells by MHCII molecules. Structural characterization of the NO-derived product PSA-NO indicates that partial deaminative depolymerization does not alter the zwitterionic nature of PSA. Unlike native PSA, PSA-NO is presented by iNOS-deficient APCs to induce CD4(+) T cell proliferation. Furthermore, metabolically active APCs are required for PSA-NO presentation. In contrast to PSA degradation by RNSs, dextran depolymerization in the endosome depends on ROSs, including hydrogen peroxide- and superoxide-derived ROSs. This study provides evidence that MHCII pathway-mediated carbohydrate antigen processing in APCs is achieved by chemical reactions. RNSs and ROSs may be involved in the presentation of glycopeptides by MHC molecules via the processing of other carbohydrate-containing antigens, such as bacterial or viral glycoproteins or glycoconjugate vaccines.
journal_name
Proc Natl Acad Sci U S Aauthors
Duan J,Avci FY,Kasper DLdoi
10.1073/pnas.0800974105subject
Has Abstractpub_date
2008-04-01 00:00:00pages
5183-8issue
13eissn
0027-8424issn
1091-6490pii
0800974105journal_volume
105pub_type
杂志文章abstract::The results of physicochemical studies of mammalian metallothioneins are summarized and used to propose a model of the protein. The primary structures of all mammalian metallothioneins are very homologous; there are 38 invariant residues and 20 of them are cysteines. The results of UV and CD optical studies indicated ...
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更新日期:1989-05-01 00:00:00