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Michael A Faust, Elizabeth Motunrayo Kolawole, Brian D Evavold, Induction with MHC variant peptide MOG 45D generates MOG-reactive T cells but no clinical disease, The Journal of Immunology, Volume 206, Issue 1_Supplement, May 2021, Page 18.06, https://doi.org/10.4049/jimmunol.206.Supp.18.06
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Abstract
Demyelinating disease can be driven by CD4+ T cells specific for myelin oligodendrocyte glycoprotein (MOG). We have previously decreased the affinity of MOG for Class II MHC by mutating the P6 anchor residue from an S to a D amino acid, creating the 45D MHC variant peptide. 45D is incapable of inducing experimental autoimmune encephalomyelitis (EAE) despite its CD4 epitope bearing the same T cell receptor contact residues as the wildtype MOG epitope (wtMOG). Although the wtMOG and 45D peptides generate CD4 T cells specific for MOG in the periphery and CNS, there is an overall decrease in the number of high-affinity CD4 T cells in response to 45D priming. Analysis of the responding T cell populations to 45D also found increases in MOG-reactive Tregs and decreases in MOG-specific CD8 T cells. Thus, the variant peptide 45D alters the MOG-specific T cell response in favor of peripheral tolerance mechanisms that ultimately result in the absence of clinical disease.
