Specificity of autoantibodies to epitopes of myelin proteins in multiple sclerosis

Permphan Dharmasaroja, Faculty of Science, Department of Anatomy, Mahidol University, 272 Rama VI Road, Rajthevi, Bangkok 10400, Thailand

From Journal of the Neurological Sciences Volume 206, Issue 1 , 15 January 2003, Pages 7-16

Abstract
An autoimmune response to one or more myelin-protein components is thought to be part of the pathogenesis of multiple sclerosis (MS). The immunodominant-autoantibody epitope may be localized on a linear peptide segment, on a conformation-sensitive epitope, or on an epitope resulting from post-translational modifications. Primary, secondary, and tertiary structures of myelin proteins may determine the specific site for binding of autoantibodies. A myelin protein-specific autoantibody can bind to either a linear or conformational epitope, whereas all of the T cell epitopes are linear. At present, the conformational epitopes of myelin proteins have not been identified; most of the methods used to identify the myelin-protein epitopes corresponding to the pathogenesis of multiple sclerosis are involved in the linear epitope mapping. Polymorphism or mutations may cause inappropriate expression of the myelin proteins with alterations to their linear and/or conformational epitopes, and make them susceptible to autoantibody binding, especially if these changes occur at the surface of the protein. This review focuses on the specificity of autoantibodies to the epitopes of myelin proteins and correlates this to the structures of proteins. Factors that influence the expression of myelin-protein epitopes such as the α-helical or β-sheet structure of the protein, the tri-proline site, and the post-translational modifications as well as physicochemical properties of amino acid changed are included.

Author Keywords: Multiple sclerosis; Myelin basic protein; Myelin proteolipid protein; Myelin oligodendrocyte glycoprotein; Immunoglobulins; Epitope mapping; Epitope specificity; Myelin proteins

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