IDENTIFICATION OF EPITOPES OF MYELIN OLIGODENDROCYTE GLYCOPROTEIN FORTHE INDUCTION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN SJL AND BIOZZI AB H MICE/

A recombinant protein corresponding to the Ig-like domain of myelin ol igodendrocyte glycoprotein (MOG) and synthetic 15-mer peptides of the whole MOG molecule with eight amino acid overlaps were screened for th eir ability to induce experimental allergic encephalomyelitis (EAE) in Biozzi AB/H (H-2(dq1)) and SJL (H-2(s)) mice. Clinical and histologic evidence of EAE developed after sensitization with the recombinant MO G protein in both AB/H and SJL mice. In AB/H mice at least three MOG e pitopes within residues 1-22, 43-57, and 134-148 induced clinical and histologic EAE, whereas only the sequence 92-106 was encephalitogenic in SJL mice. Histologically, the inflammatory response in the central nervous system consisted of perivascular accumulations of CD5(+) T cel ls and F4/80(+) macrophage/microglia cells equally distributed in the brain and spinal cord. The subpial/meningeal infiltration, characteris tic of mouse EAE induced with spinal cord homogenate, was only observe d in cases of severe clinical disease in SJL mice in which the cellula r infiltrates predominated in the spinal cord. In spite of the presenc e of histologic lesions in AB/H mice immunized with MOG, clinical dise ase either rapidly resolved or was clinically silent. In contrast to i mmunization of SJL mice with recombinant MOG, sensitization to MOG 92- 106 induced severe clinical paralysis. After recovery these animals re lapsed and exhibited demyelinated lesions. This study is the first to describe encephalitogenic epitopes of MOG that induce both clinical an d histologic signs of EAE in mice. These and previous findings implica ting MOG as a target Ag for Ab-mediated attack in EAE suggest that suc h autoreactivity to MOG may be significant in the development of human demyelinating diseases such as multiple sclerosis.