The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8(+) dendritic cells

Immunity. 2009 Apr 17;30(4):544-55. doi: 10.1016/j.immuni.2009.01.013. Epub 2009 Mar 26.

Abstract

A unique subpopulation of spleen dendritic cells (DCs) that express the CD8 surface marker efficiently present phagocytosed antigens to CD8(+) T lymphocytes in a process called "crosspresentation," which initiates cytotoxic immune responses. We now show that the small GTPase Rac2 plays a critical role in antigen crosspresentation selectively in this DC subpopulation. In CD8(+) DCs, Rac2 determines the subcellular assembly of the NADPH oxidase complex (NOX2) to phagosomes, whereas in CD8(-) DCs, Rac1 mediates the assembly of NOX2 at the plasma membrane. In the absence of Rac2, the production of reactive oxygen species (ROS) in DC-phagosomes was abolished, the phagosomal pH dropped, and the efficiency of antigen crosspresentation was reduced. We conclude that the activity of Rac1 and 2 control crosspresentation in DC subpopulations through the regulation of phagosomal oxidation and pH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8 Antigens*
  • Cells, Cultured
  • Cross-Priming
  • Dendritic Cells / immunology*
  • Fluorescent Antibody Technique
  • Hydrogen-Ion Concentration
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism
  • Phagosomes / immunology*
  • Reactive Oxygen Species / metabolism
  • rac GTP-Binding Proteins / metabolism*

Substances

  • CD8 Antigens
  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases
  • rac2 GTP-binding protein
  • rac GTP-Binding Proteins