Westphal, Maria

Abstract Description Neurons upregulate MHC Class I during infection and neuroinflammation associated with demyelinating diseases, allowing them to present both self and foreign antigens to CD8+ T cells. We hypothesized that ablation of neuronal MHC I expression reduces neural antigen-specific CD8+ T cell recruitment to demyelinated CNS and reduces neuron loss. We have previously shown that demyelination induces expression of MHC Class I on neurons and axons, allowing neuron-specific neoantigens to be presented to CD8+ T cells, leading to neuroinflammatory damage. Elevated MHC-I and β2-microglobulin expression in white and grey matter tissue from MS patients further supported the role of CD8+ T cells in neuronal injury. Here we demonstrate that neuron specific β2-microglobulin ablation in the B6 MOG35-55 EAE model of multiple sclerosis reduces disease progression and severity via clinical scoring. Our preliminary findings suggest that MHC-I ablation may reduce peripheral activation and CNS recruitment of neural antigen-specific CD8+ T cells as well as CD8+ T cell-mediated neurodegeneration in in the context of demyelinating disease. Future studies are aimed at generating a humanized mouse model reconstituted with patient immune cells to understand the role of MHC I expression in neurons, astrocytes, and oligodendrocytes. Specifically, using this model, we will characterize brain infiltrating T cells from patients with CNS autoimmune disease and suspected T cell involvement. Funding Sources Generous donation from Don and Fran Herdrich. Topic Categories Neuroimmunology (NEUR)