Suppression of experimental allergic encephalomyelitis by chemically modified encephalitogen

The results of enzymatic and chemical degradation studies of the basic myelin protein suggested that tryptophan is essential for encephalitogenic activity in the guinea pig. The object of the present investigation was to modify the protein through its tryptophan residue in such a way that it becomes non-encephalitogenic, yet suppresses experimental allergic encephalomyelitis (EAE). Accordingly, the single tryptophan residue of the protein was modified with specific reagents such as 2-hydroxy-5-nitrobenzylbromide (HNB-BR), 2-nitrophenylsulfenyl chloride (NPSCl) and performic acid. Injection of the modified proteins did not result in neurological disease, although some guinea pigs did exhibit histological changes in the brain. Starting 3 days after injection with the active inoculum, the treatment with the modified proteins was carried out for four weeks, using a total of 900 μg og the modified proteins. The guinea pigs treated with HNB and performic acid oxidized protein did not show neurological signs of the disease, but from the NPSCl group, two out of 10 developed EAE, although at a later data compared with those guinea pigs which were injected with the unmodified encephalitogen. The results not only confirm previous findings that intact tryptophan in the protein is a prime requirement for the production of EAE in guinea pigs, but also provide evidence that tryptophan is not essential for suppression of the disease. The conclusion we may draw from these studies is that the encephalitogenic basic myelin protein has two active sites: one which contains tryptophan required for the paralytic effect, the other without tryptophan which provides protection.