Abstract |
Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production. Defects in oxidase function result in chronic granulomatous disease with hallmark recurrent microbial infections and inflammation. The oxidase's role in the adaptive immune response is not well understood. Class II presentation of cytoplasmic and exogenous Ag to CD4(+) T cells was impaired in human B cells with reduced oxidase p40(phox) subunit expression. Naturally arising mutations, which compromise p40(phox) function in a chronic granulomatous disease patient, also perturbed class II Ag presentation and intracellular ROS production. Reconstitution of patient B cells with a wild-type, but not a mutant, p40(phox) allele restored exogenous Ag presentation and intracellular ROS generation. Remarkably, class II presentation of epitopes from membrane Ag was robust in p40(phox)-deficient B cells. These studies reveal a role for NADPH oxidase and p40(phox) in skewing epitope selection and T cell recognition of self Ag.
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Authors | Victoria L Crotzer, Juan D Matute, Andrés A Arias, Heng Zhao, Lawrence A Quilliam, Mary C Dinauer, Janice S Blum |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 189
Issue 8
Pg. 3800-4
(Oct 15 2012)
ISSN: 1550-6606 [Electronic] United States |
PMID | 22984083
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- HLA-DR Antigens
- Phosphoproteins
- Reactive Oxygen Species
- neutrophil cytosol factor 40K
- NADPH Oxidases
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Topics |
- Antigen Presentation
(genetics, immunology)
- B-Lymphocyte Subsets
(enzymology, immunology, metabolism)
- Cell Line, Transformed
- HLA-DR Antigens
(metabolism)
- Humans
- Intracellular Fluid
(enzymology, immunology, metabolism)
- Lymphocyte Activation
(genetics, immunology)
- NADPH Oxidases
(physiology)
- Phosphoproteins
(biosynthesis, deficiency, genetics)
- Reactive Oxygen Species
(metabolism)
- Up-Regulation
(genetics, immunology)
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