title: Altered susceptibility to EAE in congenic NOD mice: Altered processing of the encephalitogenic MOG35-55 peptide by NOR/LtJ mice.
abstract: NOD mice (H-2 g7) naturally develop autoimmune diabetes, while the congenic NOR/LtJ mice (H-2 g7) are resistant. To determine if defective immune regulation renders NOD susceptible to autoimmune disease, we compared MOG35-55-induced EAE in NOD mice to that of NOR/LtJ. In two of three immunization protocols, the NOR/LtJ mice developed significantly reduced indices and severity of clinical disease, in spite of an exaggerated autoimmune response to MOG35-55. Characterization of the responding T cell repertoires revealed that V beta 8+ Th cells directed toward the MOG42-55 core epitope were dominant in both strains. Interestingly, CD8+ CTL were absent or significantly reduced in MOG35-55 lymphoblasts from NOR/LtJ mice, which poorly processed the MOG39-47 CTL epitope from MOG35-55. Thus, while particular MHC class II alleles may be associated with increased risk, molecules involved in the processing of key epitopes may be influential in the progression of autoimmune disease.
authors.affiliation: Department of Biological Sciences, University of Toledo, 2801 W. Bancroft, Toledo, OH 43606, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Mayo
authors.forename: Anthony
authors.initials: A
authors.lastname: Quinn
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)