Altered susceptibility to EAE in congenic NOD mice: Altered processing of the encephalitogenic MOG35-55 peptide by NOR/LtJ mice.
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.
Mayo
Stella
S
Department of Biological Sciences, University of Toledo, 2801 W. Bancroft, Toledo, OH 43606, USA.
Quinn
Anthony
A
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*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)