High-throughput Multidimensional Characterization of CD8 T cells in MOG Antibody-Associated Disease

Abstract Inflammatory demyelinating diseases of the central nervous system (CNS) include clinically and pathologically distinct disorders. Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a recently characterized antibody-mediated inflammatory disorder CNS with clinical presentations which optic neuritis, transverse myelitis, acute disseminated encephalomyelitis. The heterogenous course MOGAD along unclear prognostic biomarkers makes treatment challenging, as some individuals have monophasic while others relapse. Recent work has attempted to identify by performing scRNA-seq on peripheral blood mononuclear cells (PBMC) patients highlighted an enrichment for cytotoxic effector CD8 +T cell subset in compared healthy controls. However, this remains under characterized, questions regarding their antigen specificity, clonality, overall involvement MOGAD. To further characterize subset, we utilize single technology, TetTCR-SeqHD, evaluate antigen-specificity, gene expression, surface protein expression isolated from PBMC patients. In approach, large library fluorescently labeled, DNA barcoded peptide-MHC tetramers are generated utilizing peptides derived MOG or associated proteins such myelin basic proteolipid then used isolate specific CD8+ T analysis. Preliminary results show CD161 ++TRAV1–2 +MAIT population MOGAD, been previously implicated other chronic diseases. This supported Chan Zuckerberg Initiative Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.