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More MS news articles for June 2004

A structurally available encephalitogenic epitope of myelin oligodendrocyte glycoprotein specifically induces a diversified pathogenic autoimmune response

J Immunol. 2004 Jul 1;173(1):600-6
Bischof F, Bins A, Durr M, Zevering Y, Melms A, Kruisbeek AM.
Department of Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

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.