INCREASED REACTIVITY TO MYELIN OLIGODENDROCYTE GLYCOPROTEIN PEPTIDES AND EPITOPE MAPPING IN HLA DR2(15)-SCLEROSIS( MULTIPLE)

Multiple sclerosis (MS) is a central nervous system-specific inflammat ory and demyelinating disease where a myelin-directed autoimmune respo nse is thought to be pathogenetically relevant. Myelin oligodendrocyte glycoprotein (MOG) is a surface-exposed minor myelin component that i s a prime candidate autoantigen. We have investigated peripheral blood lymphocyte responses to synthetic 15-26 amino acids long overlapping MOG peptides in 20 MS patients and 14 healthy controls with the MS-ass ociated HLA haplotype DR2(15). There were significantly increased resp onses, in terms of numbers of cells secreting IFN-gamma detected by El ispot in response to several MOG-derived peptides in the MS patients, but not the healthy controls. MOG peptide 63-87 evoked the strongest r esponse, and the stimulatory property of this peptide was confirmed in additional DR2(15)+ MS patients where a peptide concentration-depende nt proliferative response, which was inhibited by the addition of anti -HLA class II antibodies, was observed. This is the first work detaili ng putative immunodominant T cell epitopes of MOG in DR2(15)+ MS patie nts.