Autoimmune T-Cell Reactivity to Myelin Proteolipids and Glycolipids in Multiple Sclerosis

Central nervous system (CNS) myelin, the likely major target of autoimmune attack in multiple sclerosis (MS), contains a number of unique components that are potential targets of the attack. Two classes of molecules that are greatly enriched in CNS myelin compared to other parts of the body are certain types of proteolipids and glycolipids. Due to the hydrophobic nature of both of these classes of molecules, they present challenges for use in immunological assays and have therefore been somewhat neglected in studies of T-cell reactivity in MS compared to more soluble molecules such as the myelin basic proteins and the extracellular domain of myelin oligodendrocyte glycoprotein. This review firstly looks at the makeup of CNS myelin, with an emphasis on proteolipids and glycolipids. Next, a retrospective of what is known of T-cell reactivity directed against proteolipids and glycolipids in patients with MS is presented, and the implications of the findings are discussed. Finally, this review considers the question of what would be required to prove a definite role for autoreactivity against proteolipids and glycolipids in the pathogenesis of MS.