Oligodendrocyte-specific protein peptides induce experimental autoimmune encephalomyelitis in SJL J mice

Oligodendrocyte-specific protein (OSP) is a recently isolated and cloned, 2 07-aa, hydrophobic, four-transmembrane protein found in CNS myelin, It repr esents similar to 7% of total myelin protein. The OSP cDNA sequence has no significant homology with previously reported genes, but the predicted prot ein structure suggests that OSP is a CNS homologue of peripheral myelin pro tein-22, We previously reported the presence of anti-OSP Abs in the cerebro spinal fluid of relapsing-remitting multiple sclerosis (MS) patients, but n ot control patient groups. In this study, we tested the ability of a panel of 20-mer peptides with 10-aa overlaps, representing the sequence of murine OSP, to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. SJL mice challenged with murine OSP peptides 52-71, 82-101, 1 02-121, 142-161, 182-201, and 192-207 exhibited clinical EAE, OSP:52-71 eli cited severe relapsing-remitting EAE in some individuals. All other encepha litogenic peptides elicited, at most, a loss of tail tonicity from which th e mice most often completely recovered. Mononuclear cell infiltrates and fo cal demyelination characteristic of EAE were evident. T cell proliferative responses were seen with all encephalitogenic peptides except 142-161 and 1 82-201. OSP peptides 72-91 and 132-151 did not cause clinical EAE, but did elicit robust proliferative responses. BIO,PL and PL/J mice challenged with the same OSP peptide doses as SJL mice did not exhibit clinical EAE, These results in the SJL EAE model, together with the results from MS patient cl inical samples, make OSP a promising candidate for autoantigenic involvemen t in MS.