The Small GTPase Rac2 Controls Phagosomal Alkalinization and Antigen Crosspresentation Selectively in CD8+ Dendritic Cells

被引：221

作者：

Savina, Ariel ^{[1
]}

Peres, Audrey ^{[1
]}

Cebrian, Ignacio ^{[1
]}

Carmo, Nuno ^{[2
]}

Moita, Catarina ^{[2
]}

Hacohen, Nir ^{[3
,4
,5
]}

Moita, Luis F. ^{[2
]}

Amigorena, Sebastian ^{[1
]}

机构：

[1] Inst Curie, INSERM U653, F-75248 Paris 05, France

[2] Univ Lisbon, Fac Med, Inst Mol Med, Cell Biol Immune Syst Unit, P-1649028 Lisbon, Portugal

[3] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA

[4] Broad Inst Harvard, Cambridge, MA 02142 USA

[5] MIT, Cambridge, MA USA

来源：

IMMUNITY | 2009年 / 30卷 / 04期

关键词：

NUCLEOTIDE EXCHANGE FACTOR; PHAGOCYTE NADPH OXIDASE; IN-VIVO; CROSS-PRESENTATION; PRESENTING CELLS; RHO-GTPASES; MURINE MACROPHAGES; CATHEPSIN-S; ACTIVATION; LOCALIZATION;

D O I：

10.1016/j.immuni.2009.01.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 Racl and 2 control crosspresentation in DC subpopulations through the regulation of phagosomal oxidation and pH.

引用

页码：544 / 555

页数：12

共 44 条

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