A structurally available encephalitogenic epitope of myelin oligodendrocyte glycoprotein specifically induces a diversified pathogenic autoimmune response.
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.
Bischof
Felix
F
Department of Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Felix.Bischof@uni-tuebingen.de
Bins
Adriaan
A
Dürr
Michael
M
Zevering
Yinka
Y
Melms
Arthur
A
Kruisbeek
Ada M
AM
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments