Encephalitogenic and immunogenic potential of myelin-associated glycoprotein (MAG), oligodendrocyte-specific glycoprotein (OSP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in ABH and SJL mice.
Synthetic peptides of myelin-associated glycoprotein (MAG), oligodendrocyte-specific glycoprotein (OSP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were screened for their ability to induce experimental allergic encephalomyelitis (EAE) in ABH (H-2A(g7)) and SJL (H-2(s)) mice. The use of overlapping 16mer MAG peptides identified residues 97-112 as a T-cell and encephalitogenic epitope in ABH mice which induced clinical and histological signs of acute EAE. Immunization of SJL mice with MAG peptides failed to induce disease whereas immunization of SJL mice with synthetic peptides of OSP induced major T-cell responses to OSP 73-88 and 81-96. Another epitope, OSP 57-72, that induced EAE, failed to induce T-cell responses in mice immunised with peptides based on the whole sequence supporting a role for cryptic epitopes. In comparison, whilst immunization of ABH mice with OSP revealed two immunodominant T-cell epitopes (49-64 and 137-152), an encephalitogenic epitope was not identified. Similarly, immunization of both SJL and ABH mice with CNPase peptides induced T-cell responses to several epitopes. However, these were not encephalitogenic. This study is the first to identify an encephalitogenic epitope of MAG and immunodominant epitopes of MAG, OSP and CNPase in SJL and ABH mice. The ability of both cryptic and noncryptic peptide epitopes of these myelin antigens to initiate EAE suggests that mice at least are not tolerant to some regions of MAG and OSP and that such specific autoimmune responses may play an important role in the pathogenesis of immune-mediated neurological diseases such as multiple sclerosis.
Morris-Downes
Margaret M
MM
Department of Neuroinflammation, Imperial College School of Medicine, Charing Cross Campus, Fulham Palace Road, London, UK.
McCormack
Kirsty
K
Baker
David
D
Sivaprasad
Dinesh
D
Natkunarajah
Janahan
J
Amor
Sandra
S
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D057167:Claudins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D007114:Immunization; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology
D057167:Claudins; C492354:Cldn11 protein, mouse; D000939:Epitopes; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases