Sorting and recycling endosomes during antigen cross-presentation: the role of Rab22a

IGNACIO CEBRIÁN; NICOLAS BLANCHARD; CRISTINA CROCE; LUIS MAYORGA; NÉSTOR GUERRERO

Salamanca

Workshop; EMBO Workshop: Antigen processing and presentation; 2017

EMBO

Cross-presentation by MHC-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 study, we focus on the small GTPase Rab22a which associates with tubular recycling intermediates containing MHC-I. Moreover, it is considered that the active/inactive states of Rab22a are required for tubule formation and the final fusion of these tubules with the plasma membrane. Here we identify 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 knock-down 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.