NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells

Cell, 126, 205-218 (2006)

Speaker: 顏嘉良                          Place: Room 601

Commentator: 凌斌老師                    Date: 2006/9/27 14:00-15:00

Abstract:

  Antigen-presenting cells (APCs) internalize antigens, process them in phagosomes, and present antigen-derived peptides to CD4⁺ T cells; or to CD8⁺ T cells, a process called crosspresentation.  Internalized antigen in phagosomes will be degraded into small fragments that become lodged in the peptide binding grooves of MHC molecules.  Previous findings showed that partial degradation of antigen in dendritic cell (DC) phagosomes compared with macrophages can promote antigen presentation via MHC class II molecules.  This paper addressed the question whether antigen crosspresentation by DCs is promoted by the attenuation of the proteolytic environment found in DC phagosomes.  Firstly, the authors showed that the phagosomes of DCs maintained a neutral, even slightly alkaline pH in contrast to macrophage phagosomes, which have an acidic condition in their phagosomes.  This phagosome neutralization involves NADPH oxidase, NOX2, producing reactive oxygen species (ROS) to neutralize the pH, and modulate protease activity to prevent fully degradation of exogenous antigen.  In DCs lacking a key membrane component of the oxidase, gp91phox, they failed to alkalize phagosomes and degrade phagocytosed antigen more rapidly.  Secondly, the authors found that crosspresentation of antigen was much less efficient in gp91-deficient DCs compared with wild-type DCs. These findings revealed that ROS produced by NOX2 can neutralize phagosomal pH and build an environment that prefers partial degradation of exogenous antigen and promotes crosspresentation. This paper gives us another evidence that DCs, compared with macrophages, are professional APCs which promote antigen presentation at different level.

References:

1.          Le´lia Delamarre, et al. Differential Lysosomal Proteolysis in Antigen-Presenting Cells Determines Antigen Fate. Science 307, 1630-1634 (2005)

2.          Ariel Savina, et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell, 126, 205-218 (2006)