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The phagosome and redox control of antigen processing
Benjamin W Ewanchuk1, Robin M Yates2
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1.
Free Radical Biology & Medicine
|March 27, 2018
Summary
Phagosome redox balance influences antigen processing, altering T cell responses. Manipulating NADPH oxidase (NOX2) and GILT impacts peptide repertoires, affecting autoimmunity and tolerance.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Phagosomes are crucial for antigen processing in antigen-presenting cells.
- Lumenal biochemistry, particularly redox state, significantly impacts peptide epitope composition and immunodominance.
- While human leukocyte antigen (HLA) haplotypes are studied, phagosomal redox is an emerging determinant.
Purpose of the Study:
- To review the mechanisms and consequences of redox-mediated phagosomal antigen processing.
- To explore the downstream implications for immune tolerance and autoimmunity.
Main Methods:
- Focuses on the impact of lumenal redox microenvironment on proteolysis and disulfide reduction.
- Discusses manipulation of phagosomal oxidative and reductive capacities.
- Highlights the roles of NADPH oxidase (NOX2) and γ-interferon-inducible lysosomal thiol reductase (GILT).
Main Results:
- Altered phagosomal redox balance modifies antigen processing patterns.
- Changes in peptide repertoires available for presentation are observed.
- Modified peptide repertoires lead to altered disease progression in T cell-driven autoimmunity.
Conclusions:
- Phagosomal redox state is a critical factor in determining antigenic peptide repertoires.
- Modulating NOX2 and GILT activities can influence immune responses.
- Understanding redox-mediated processing offers potential therapeutic strategies for autoimmunity and tolerance induction.
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