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