Rab22a controls MHC‐I intracellular trafficking and antigen cross‐presentation by dendritic cells. (10th October 2016)

• Record Type: Journal Article
• Authors: Cebrian, Ignacio; Croce, Cristina; Guerrero, Néstor A; Blanchard, Nicolas; Mayorga, Luis S
• Is Part Of: EMBO reports. Volume 17:Number 12(2016:Dec.)
• Page Start: 1753
• Page End: 1765
• Publication Date: 2016-10-10
• Subjects: cross‐presentation -- dendritic cells -- MHC‐I molecules -- small GTPase Rab22a -- Toxoplasma gondii; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201642358
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Cross‐presentation by MHC class I molecules allows the detection of exogenous antigens by CD8 + T lymphocytes. This process is crucial to initiate cytotoxic immune responses against many pathogens (i.e., Toxoplasma gondii ) and tumors. To achieve efficient cross‐presentation, dendritic cells (DCs) have specialized endocytic pathways; however, the molecular effectors involved are poorly understood. In this work, we identify the small GTPase Rab22a as a key regulator of MHC‐I trafficking and antigen cross‐presentation by DCs. Our results demonstrate that Rab22a is recruited to DC endosomes and phagosomes, as well as to the vacuole containing T. gondii parasites. The silencing of Rab22a expression did not affect the uptake of exogenous antigens or parasite invasion, but it drastically reduced the intracellular pool and the recycling of MHC‐I molecules. The knockdown of Rab22a also hampered the cross‐presentation of soluble, particulate and T. gondii ‐associated antigens, but not the endogenous MHC‐I antigen presentation through the classical secretory pathway. Our findings provide compelling evidence that Rab22a plays a central role in the MHC‐I endocytic trafficking, which is crucial for efficient cross‐presentation by DCs. Synopsis: Cross‐presentation by MHC class I molecules allows the detection of exogenous antigens and is crucial to initiate cytotoxic immune responses against many pathogens. This report identifies the small GTPase Rab22a as a key regulator of MHC‐I trafficking and antigen cross‐presentation in dendritic cells. Endosomes, phagosomes, and Toxoplasma gondii ‐containing vacuoles of dendritic cells are decorated with endogenous Rab22a. Silencing of Rab22a expression reduces the intracellular pool of MHC‐I, preventing phagosomal acquisition and their recycling to the plasma membrane. Rab22a knockdown impairs the cross‐presentation of soluble, particulate and T. gondii ‐associated antigens, but not endogenous MHC‐I antigen presentation pathways. Abstract : Cross‐presentation by MHC class I molecules allows the detection of exogenous antigens and is crucial to initiate cytotoxic immune responses against many pathogens. This report identifies the small GTPase Rab22a as a key regulator of MHC‐I trafficking and antigen cross‐presentation in dendritic cells.