ANTIBODY-RESPONSE IN LEWIS RATS INJECTED WITH MYELIN OLIGODENDROCYTE GLYCOPROTEIN DERIVED PEPTIDES

Previous studies from our laboratory have demonstrated a predominant r esponse to myelin oligodendrocyte glycoprotein (MOG) in patients with multiple sclerosis (MS) and showed that this molecule is able to induc e in Lewis rats a chronic relapsing MS-like disease with extensive dem yelination, To further study the possibility that MOG is a primary tar get antigen in MS, we have begun to investigate the encephalitogenicit y and antibody response of different sequences of the extracellular do mains of MOG in Lewis rats, Vile report that none of the synthetic pep tides encompassing the MOG amino acid sequences 1-21, 67-87, 104-117 a nd 202-218 were encephalitogenic. In contrast, a single injection of M OG35-55 was able to induce severe neurological signs associated with i nflammation and demyelination. All rats injected with MOG peptides 1-2 1, 35-55, 67-87 and 202-218 developed a high level of antibodies to th eir respective immunizing peptides as detected by ELISA and immunoblot ting, Although all MOG peptide antisera reacted with immunoblots of na tive MOG separated under reducing conditions, only anti-MOG35-55 and a nti-MOG202-218 antibodies reacted to native MOG, when tested under non reducing conditions, These results indicate that the MOG35-55 peptide, which is found in the extracellular Ig V-like domain of MOG, is not o nly an encephalitogenic epitope but could also be an important determi nant for initiating antibody-mediated demyelination. As indicated by t he absence of reactivity to the other MOG peptides tested, as well as other central nervous system myelin proteins including myelin basic pr otein and proteolipid protein, the antibody response produced by MOG p eptides is highly restricted.