Differential expression of a novel candidate auto-antigen, X2 MBP, in multiple sclerosis (MS) lesions

The recent identification of T cells reactive to the peptide encoded by exon 2 of the myelin protein gene (X2 MBP) in patients with multiple sclerosis (MS) has focused attention on MBP isoforms harboring peptides which might serve as autoantigens. X2 MBP is included in the 21.5 kDa isoform of MBP and is normally only expressed during myelinogenesis. To investigate whether X2 MBP expression is associated vith remyelination and regenerated oligodendrocytes, the present study has compared X2 MBP expression in MS lesions with different degrees of activity. Chronic silent, chronic active and acute lesions were studied for X2 MBP expression by in situ hybridization utilizing a synthetic oligonucleotide anti-sense probe for X2 MBP (nucleotides 238-285) labeled with [35S]-dATP, and the sense probe as a negative control. The results have shown that in chronic MS lesions mRNA X2 MBP-positive oligodendrocytes were localized along the edge of the lesion which was partially remyelinated. In chronic active MS lesions mRNA X2 MBP positive cells were detectable with a more scattered distribution. No significant X2 MBP reactivity was found in acute lesions, as well as in normal white matter. These findings suggest that X2 MBP is expressed by a population of recently generated oligodendrocytes arising subsequently to myelin breakdown, probably associated with remyelination. The prevalence of X2 MBP in chronic lesions raises the possibility that this peptide may play a role in the perpetuation of the disease by epitope spreading.