Human transaldolase and cross-reactive viral epitopes identified by autoantibodies of multiple sclerosis patients

Multiple sclerosis is mediated by an autoimmune process causing selective d estruction of oligodendrocytes, Transaldolase, which is expressed in the br ain selectively in oligodendrocytes, is a target of high affinity autoantib odies in serum and cerebrospinal fluid of multiple sclerosis patients. A th ree-dimensional model of human transaldolase was developed based on the cry stal structure of the enzyme from Escherichia coli. To identify immunodomin ant epitopes, 33 peptides overlapping human transaldolase by 5 amino acids were synthesized. Ab 12484, raised against enzymatically active human trans aldolase, recognized antigenic determinants corresponding to linear epitope s (residues 27-31 and 265-290) and rx helices (residues 75-98 and 302-329), Four immunodominant peptides harboring charged amino acid residues with to pographically exposed side chains were identified by sera from 13 multiple sclerosis patients with predetermined autoreactivity to transaldolase, Auto antibodies binding to the most prominent human transaldolase epitope, betwe en residues 271 and 285, showed cross-reactivity with Epstein-Barr and herp es simplex virus type 1 capsid-derived peptides. Molecular mimicry between immunodominant autoepitopes and viral Ags may be a decisive factor in direc ting autoimmunity to transaldolase in multiple sclerosis patients.