T-CELL RESPONSES TO MYELIN ANTIGENS IN MULTIPLE-SCLEROSIS - RELEVANCEOF THE PREDOMINANT AUTOIMMUNE REACTIVITY TO MYELIN OLIGODENDROCYTE GLYCOPROTEIN

Until recently, the search for the 'culprit' autoantigen towards which deleterious autoimmunity is directed in multiple sclerosis (MS) cente red mostly on myelin basic protein (MBP) and proteolipid (PLP), the tw o most abundant protein components of central nervous system (CNS) mye lin, the target tissue for the autoimmune attack in MS. Although such research has yielded important data, furthering our understanding of t he disease and opening avenues for possible immune-specific therapeuti c approaches, attempts to unequivocally associate MS with MBP or PLP a s primary target antigens in the disease have not been successful. Thi s has led in recent years to a new perspective in MS research, whereby different CNS antigens are being investigated for their possible role in the initiation or progression of MS. Interesting studies in labora tory animals show that T-cells directed against certain non-myelin-spe cific CNS antigens are able to cause inflammation of the CNS, albeit w ithout expression of clinical disease. However, reactivity to these an tigens by MS T-cells has not been demonstrated. Conversely, reactivity by MS T-cells to non-myelin-specific antigens such as heat shock prot eins, could be observed, but the pathogenic potential of such reactivi ty has not been corroborated with the encephalitogenicity of the antig en. More relevant to MS pathogenesis may be, as we outlined in this re view, the autoimmune reactivity directed against minor myelin proteins , in particular the CNS-specific myelin oligodendrocyte glycoprotein ( MOG). Here, we review the current knowledge gathered on T-cell reactiv ity to possible target antigens in MS in the context of their encephal itogenic potential, and underline the facets which make MOG a highly r elevant contender as primary target antigen in MS, albeit not necessar ily the only one. (C) 1998 Academic Press.