Conditional MHC class I deletion in Tmem119+ microglia attenuates the brain infiltrating virus antigen specific CD8 T cell response.

Abstract

Microglia activation is a hallmark feature of the immune response associated with neurological disease. In neuropathological conditions, microglia become fully competent antigen presenting cells and are proposed to perpetuate T cell activation in the brain. Historically, it has been difficult to define the extent microglia enhance CD8 T cell responses in the brain through MHC class I restricted antigen presentation. Using a novel single MHC Class I Cre Lox approach developed by our laboratory in which H-2Kb can be deactivated in Tmem119+ cells, we were able to determine the role of microglial MHC class I following intracranial (i.c.) administration of Theiler’s murine encephalomyelitis virus (TMEV) encoding the model antigen OVA. After confirming the successful deletion of H-2Kb in Tmem119+ cells using spectral flow cytometry, we investigated antigen-specific CD8 T cell expansion and the response of other immune cells in the brain and blood at 7 days post i.c. TMEV-OVA infection. We observed a marked reduction in Kb:OVA epitope specific CD8 T cells in the brain in Tmem119-cre Kb cKO mice compared to Cre- controls. This reduction in in Kb:OVA epitope specific CD8 T cells was not observed outside the CNS. Our results support a role for microglia MHC class I restricted antigen presentation for complete T cell expansion in the brain, implicating this process in protective and pathogenic neurologic conditions.