ANALYSIS OF THE FINE B-CELL SPECIFICITY DURING THE CHRONIC RELAPSING COURSE OF A MULTIPLE-SCLEROSIS-LIKE DISEASE IN LEWIS RATS INJECTED WITH THE ENCEPHALITOGENIC MYELIN OLIGODENDROCYTE GLYCOPROTEIN PEPTIDE-35-55/

We have recently shown that a single injection of myelin oligodendrocy te glycoprotein (MOG), or the MOG(35-55) peptide, produces a relapsing -remitting neurologic disease with extensive plaque-like demyelination . Given the features that this new autoimmune demyelinating model has in common with the clinicopathologic manifestations of multiple sclero sis, we have examined the Ab reactivity to native MOG and MOG(35-55) p eptide during the course of the disease in Lewis rats. Following immun ization with MOG(35-55), varied clinical symptoms were observed; these included hind and foreleg paralysis and various degrees of balance im pairment. Disease progression also varied: 3 out of 21 animals had a s ingle mild disease episode; 4 out of 21 had a mild relapsing-remitting disease; and 14 out of 21 had severe relapsing-remitting disease. Ab reactivity to MOG(35-55) and native MOG was first detected in all rats 4 wk postimmunization and persisted throughout the 12 wk of observati on. The Ab response was highly restricted with no reactivity to other peptides encompassing different extracellular segments of MOG. Fine ep itope mapping showed that Ab from serum and cerebrospinal fluid of inj ected rats reacted strongly to MOG(37-46) and to a lesser extent to MO G(43-50). Although significant levels of anti-MOG Abs appeared necessa ry for the development of demyelinating lesions, their presence in blo od and cerebrospinal fluid alone was not sufficient to produce severe clinical symptoms. These results demonstrate that the MOG(35-55) pepti de is highly encephalitogenic and can induce strong T and B cell respo nses. It is probably the complex interaction between these T and B cel ls that determines the severity of disease in individual rats.