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

Authors

Aaron Johnson, Marina Seady, Mark Maynes, Javonte Thelwell, Fang Jin, Michael Hansen, Hadley Jensen, Ryann Witter, Carley Owens, Asma Hassani, Cody Lewis, Michael Forston

Published in

Research square. Jun 24, 2026. Epub Jun 24, 2026.

Abstract

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-2K ^b and H-2D ^b Tmem119 conditional knockout mice. During TMEV infection, we determined using Tmem119 K ^b cKO mice that microglia H-2K ^b contributes to antiviral CD8 T cell proliferation in the brain. Meanwhile, using Tmem119 D ^b cKO mice we determined that microglia H-2D ^b increased antiviral CD8 T cell perforin levels and the capacity to induce blood-brain barrier (BBB) disruption. Furthermore, microglial H-2D ^b 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.

PMID:
42396480
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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