MOG-specific T cells skew high affinity during severe demyelinating disease after recombinant protein induction

Abstract Demyelinating diseases can be driven by CD4 T cells specific for self-antigen derived from myelin in the central nervous system (CNS). Mouse models utilizing peptide induction protocols may restrict breadth of cell specificity. Here, we compare mice induced with a fragment oligodendrocyte glycoprotein (MOG), recombinant extracellular domain (ECD), and full-length MOG protein, which includes transmembrane domain. We sought to understand why suffer more severe demyelinating disease than those focusing on MOG-specific CNS. Fluorescently-labeled peptide-MHC tetramers revealed that ECD protein have greater frequency tetramer-positive induction. To precisely define response, employed two-dimensional micropipette adhesion assay (2D-MP), which, unlike tetramer, identifies low-affinity antigen-specific cells. confirm 2D-MP all three protocols; however, had lower peptide, likely due epitope within region. also unveiled primed skew high-affinity as compared peptide. Ultimately, our data indicate after is posit this change antigen presentation priming. 5R01NS071518-09 5R01AI110113-05