title: An MHC anchor-substituted analog of myelin oligodendrocyte glycoprotein 35-55 induces IFN-gamma and autoantibodies in the absence of experimental autoimmune encephalomyelitis and optic neuritis.
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-gamma 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.
authors.affiliation: Department of Microbiology and Immunology, Emory University, Atlanta 30322, USA.
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
authors.forename: Brian D
authors.initials: BD
authors.lastname: Evavold
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D009902:Optic Neuritis / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D006023:Glycoproteins; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D007376:Interleukin-2; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; C445081:myelin oligodendrocyte glycoprotein (35-55); D015847:Interleukin-4; D007371:Interferon-gamma