A Role for NADPH Oxidase in Antigen Presentation

Gail J Gardiner,Sarah N Deffit,Shawna Mcletchie,Crystal C Walline,Liliana Pérez,Janice S Blum

doi:10.3389/fimmu.2013.00295

Abstract

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.−). This radical is an important precursor of hydrogen peroxide (H2O2) and other reactive oxygen species needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC) crosspresentation by major histocompatibility complex class I molecules through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules.

Highlights

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.−)
Given that crosspresentation of the long, but not short, MelanA/MART-1 peptide requires processing by dendritic cell (DC), these results indicate an important role for NADPH oxidase in antigen processing and crosspresentation by human DC [37]
Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD), a primary immunodeficiency that has been linked with a number of autoinflammatory and autoimmune disorders

Summary

Introduction

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.−). Loss of ovalbumin on coated beads after phagocytosis suggested enhanced degradation of this antigen in gp91phox-deficient cells compared with wild type DC, consistent with a role for the oxidase in limiting antigen processing for crosspresentation [36]. Using an assay with bead coupled cysteine-linked fluorochromes, disulfide bond reducing capacity was found to be markedly inhibited within phagosomes of wild type DC compared to gp91phox-deficient DC, suggesting NADPH oxidase activity may be important for regulating disulfide bond reduction in antigen processing events [40].

Results

Conclusion