Encephalitogenic epitopes of myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein for experimental allergic encephalomyelitis induction in Biozzi ABH (H-2Ag7) mice share an amino acid motif.
Myelin basic protein (MBP) and synthetic MBP peptides were screened for their ability to induce experimental allergic encephalomyelitis in Biozzi ABH (H-2Ag7) mice. In contrast to the failure of native MBP to induce experimental allergic encephalomyelitis, the use of overlapping MBP peptides revealed epitopes within MBP 12-26 and MBP 21-35, which induced mild disease. In comparison with disease induced by spinal cord homogenate or peptides of myelin oligodendrocyte glycoprotein (MOG) or proteolipid protein (PLP), the low incidence indicates that, at least in ABH mice, MBP is a minor encephalitogen. However, the data suggest the presence of a peptide core between MBP 21-26 (HARHGF), which contains similar elements to the previously defined encephalitogenic MOG 1-22 and PLP 56-70 peptides. The fine specificity of these epitopes was further investigated using frame-shifted peptides, which indicated cores between MOG 9-15 (GYPIRAL) and PLP 62-68 (NVIHAFQ). Based on these pathogenic peptides, a putative H-2Ag7 binding motif is suggested that contains a series of hydrophobic, basic, small, and large hydrophobic residues within a 6 to 7 amino acid core. The core and particular importance of these four residues in PLP 56-70 was confirmed in vitro using amino acid substitution studies. These findings support many of the predictions made by computer modeling of peptide:H-2Ag7 interactions. This may have relevance in the design of strategies in the treatment of experimental autoimmune diseases in animals that express this haplotype.
Amor
S
S
Department of Immunology, Rayne Institute, London, United Kingdom.
O'Neill
J K
JK
Morris
M M
MM
Smith
R M
RM
Wraith
D C
DC
Groome
N
N
Travers
P J
PJ
Baker
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000633:toxicity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology
D000954:Antigens, Surface; D000939:Epitopes; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein