TMEM119+ microglia MHC class I restricted antigen presentation impacts CD8 T cell memory, effector status, and blood-brain barrier disruption during neurotropic virus infection.

The impact of microglia antigen presentation on CNS infiltrating CD8 T cells responses during neurotropic virus infection remains undefined. Using Theiler's murine encephalomyelitis virus (TMEV) infection of neurons as a model system, we generated H-2Kb and H-2Db Tmem119 conditional knockout mice. During TMEV infection, we determined using Tmem119 Kb cKO mice that microglia H-2Kb contributes to antiviral CD8 T cell proliferation in the brain. Meanwhile, using Tmem119 Db cKO mice we determined that microglia H-2Db increased antiviral CD8 T cell perforin levels and the capacity to induce blood-brain barrier (BBB) disruption. Furthermore, microglial H-2Db was essential for antigen-specific reactivation of CD8 tissue resident memory (TRM) cell recall responses and BBB disruption long after virus had been cleared. These findings demonstrate discrete roles of individual MHC class I genes on microglia in CD8 T cell proliferation, effector functions, memory recall and neuropathology.