A Structurally Available Encephalitogenic Epitope of Myelin Oligodendrocyte Glycoprotein Specifically Induces a Diversified Pathogenic Autoimmune Response

Abstract

Multiple sclerosis is an inflammatory disease of the CNS that involves immune reactivity against myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the outer surface of CNS myelin. The epitope MOG92–106 is a DR4-restricted Th cell epitope and a target for demyelinating autoantibodies. In this study, we show that the immune response elicited by immunization with this epitope is qualitatively different from immune responses induced by the well-defined epitopes myelin basic protein (MBP) 84–96 and proteolipid protein (PLP) 139–151. Mice with MOG92–106-, but not with MBP84–96- or PLP139–151-induced experimental autoimmune encephalomyelitis developed extensive B cell reactivity against secondary myelin Ags. These secondary Abs were directed against a set of encephalitogenic peptide Ags derived from MBP and PLP as well as a broad range of epitopes spanning the complete MBP sequence. The observed diversification of the B cell reactivity represents a simultaneous spread toward a broad range of antigenic epitopes and differs markedly from T cell epitope spreading that follows a sequential cascade. The Abs were of the isotypes IgG1 and IgG2b, indicating that endogenously recruited B cells receive help from activated T cells. In sharp contrast, B cell reactivity in MBP84–96- and PLP139–151-induced experimental autoimmune encephalomyelitis was directed against the disease-inducing Ag only. These data provide direct evidence that the nature of the endogenously acquired immune reactivity during organ-specific autoimmunity critically depends on the disease-inducing Ag. They further demonstrate that the epitope MOG92–106 has the specific capacity to induce a widespread autoimmune response.

Beneficial actions of oleanolic acid in an experimental model of multiple sclerosis: A potential therapeutic role

“…Consistent with what has previously been reported, we found in this study that MOG-induced EAE showed higher concentrations of anti-MOG IgG antibodies of the IgG1 isotype than of the IgG2a isotype [40,41]. The continuous administration of OA (OA1 and OA2) significantly reduced IgG MOG antibody production,…”

Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale

“…In the sera of EAE developing mice anti-MBP-autoantibodies are also detected, even if EAE was induced by antigens, unrelated to MBP [5]. Over the last two decades, the role of autoantibodies in MS progression as well as their application as tools for diagnostic and prognostic criteria of the disease remains controversial [6].…”

Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy

“…Some of the mimicking B cell epitopes of MBP (MBP 98-104; MBP 85-98; MBP 99-104 ) were found to be in the immunodominant region of MBP which is MBP 85-101 . MBP 85-101 is found to be encephalitogenic peptide [29,30,6]. Hence, these mimicking B cell epitopes might be responsible for demyelination of nerves in leprosy patients.…”