Rab22a controls MHC-I intracellular trafficking and antigen cross-presentation by dendritic cells.
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.
['Cebrian|Ignacio|I|0000-0001-6505-0875', 'Croce|Cristina|C|', 'Guerrero|Néstor A|NA|', 'Blanchard|Nicolas|N|', 'Mayorga|Luis S|LS|0000-0002-5995-0671']
D000818:Animals D017951:Antigen Presentation D001854:Bone Marrow Cells D018414:CD8-Positive T-Lymphocytes D002352:Carrier Proteins D045142:Cross-Priming D004268:DNA-Binding Proteins D003713:Dendritic Cells D004705:Endocytosis D011992:Endosomes D005786:Gene Expression Regulation D015395:Histocompatibility Antigens Class I D051379:Mice D009687:Nuclear Proteins D010588:Phagosomes D021381:Protein Transport D016601:RNA-Binding Proteins D014122:Toxoplasma D014617:Vacuoles
dendritic cells Toxoplasma gondii small GTPase Rab22a MHC‐I molecules cross‐presentation