ENCEPHALITOGENIC EPITOPES OF MYELIN BASIC-PROTEIN, PROTEOLIPID PROTEIN, AND MYELIN OLIGODENDROCYTE GLYCOPROTEIN FOR EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS INDUCTION IN BIOZZI ABH (H-2A(G7)) MICE SHARE AN AMINO-ACID MOTIF

Myelin basic protein (MBP) and synthetic MBP peptides were screened fo r their ability to induce experimental allergic encephalomyelitis in B iozzi ABH (H-2A(g7)) mice. In contrast to the failure of native MBP to induce experimental allergic encephalomyelitis, the use of overlappin g MBP peptides revealed epitopes within MBP 12-26 and MBP 21-35, which induced mild disease, In comparison with disease induced by spinal co rd homogenate or peptides of myelin oligodendrocyte glycoprotein (MOG) or proteolipid protein (PLP), the low incidence indicates that, at le ast in ABH mice, MBP is a minor encephalitogen, However, the data sugg est the presence of a peptide core between MBP 21-26 (HARHGF), which c ontains similar elements to the previously defined encephalitogenic MO G 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 th ese pathogenic peptides, a putative H-2A(g7) binding motif is suggeste d that contains a series of hydrophobic, basic, small, and large hydro phobic residues within a 6 to 7 amino acid core, The core and particul ar importance of these four residues in PLP 56-70 was confirmed in vit ro using amino acid substitution studies, These findings support many of the predictions made by computer modeling of peptide:H-2A(g7) inter actions. This may have relevance in the design of strategies in the tr eatment of experimental autoimmune diseases in animals that express th is haplotype.