An MHC anchor‐substituted analog of myelin oligodendrocyte glycoprotein 35–55 induces IFN‐γ and autoantibodies in the absence of experimental autoimmune encephalomyelitis and optic neuritis

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Abstract
Previous strategies to ameliorate experimental autoimmune encephalitis (EAE) include the treatment of autoreactive T cells with altered peptide ligands, which contain amino acid substitutions at TCR contact residues. We recently showed that a variant of myelin oligodendrocyte glycoprotein (MOG) 35–55 possessing low affinity for MHC (45D) induced anergy in MOG 35–55‐specific T cells and reduced their encephalitogenicity upon adoptive transfer. Here we investigate the characteristics of the primary immune response to this MHC anchor‐substituted peptide. Overall, we observed that immunization with 45D resulted in the production of IFN‐γ and anti‐MOG 35–55 autoantibodies at levels similar to those of MOG 35–55‐immunized mice with active EAE. However, no symptoms of clinical or histological EAE or overt histological optic neuritis were observed in 45D‐immunized mice. Consistent with this finding, 45D‐immunized mice did not exhibit CD4+ infiltrates into the CNS. Therefore, MOG 35–55‐specific precursors stimulated with a weak ligand (45D) mediate some EAE‐associated effector functions but are unable to fully initiate the inflammatory process in the central nervous system that leads to clinical manifestation of EAE.

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