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Updated: Jul 6, 2026
12:48
Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
Microbial carbohydrate depolymerization by antigen-presenting cells: deamination prior to presentation by the MHCII
Jinyou Duan1, Fikri Y Avci, Dennis L Kasper
1Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Summary
Antigen-presenting cells process carbohydrates using reactive nitrogen and oxygen species. This mechanism, involving deamination by nitric oxide, is crucial for presenting carbohydrate antigens to T cells via MHCII molecules.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Exogenous proteins are degraded into peptides by proteases within antigen-presenting cells (APCs) for presentation.
- The processing of exogenous carbohydrates within APCs, particularly polysaccharides like PSA, remained less understood.
- Previous work indicated a role for inducible nitric oxide synthase (iNOS) in polysaccharide depolymerization.
Purpose of the Study:
- To elucidate the chemical mechanisms by which APCs depolymerize carbohydrates.
- To investigate the roles of reactive nitrogen species (RNSs) and reactive oxygen species (ROSs) in carbohydrate processing.
- To understand how processed carbohydrates are presented to T cells via MHC class II (MHCII) molecules.
Main Methods:
- Analysis of polysaccharide A (PSA) depolymerization by various RNSs and ROSs within APC endosomes/lysosomes.
- Structural characterization of NO-derived PSA products (PSA-NO).
- Assessment of T cell proliferation induced by native PSA versus PSA-NO presented by APCs, including iNOS-deficient APCs.
Main Results:
- Deamination by RNSs is the primary mechanism for PSA processing in APCs, essential for MHCII presentation.
- PSA-NO, a deaminated product, is presented by APCs to induce CD4(+) T cell proliferation, independent of iNOS in APCs.
- Dextran depolymerization relies on ROSs, contrasting with RNS-mediated PSA processing, highlighting distinct chemical pathways.
Conclusions:
- APC carbohydrate antigen processing for MHCII presentation occurs via specific chemical reactions involving RNSs and ROSs.
- Deamination by RNSs is a key step in processing certain carbohydrate antigens like PSA.
- These reactive species may also mediate the presentation of other complex carbohydrate-containing antigens, including those in vaccines.
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