CITRULLINE-CONTAINING MYELIN BASIC-PROTEIN IS RECOGNIZED BY T-CELL LINES DERIVED FROM MULTIPLE-SCLEROSIS PATIENTS AND HEALTHY-INDIVIDUALS

The cause of MS is uncertain, but an autoimmune disorder of the CNS is likely, and myelin basic protein (MBP) is a candidate antigen. MBP ex ists in different isoforms, generated by differential splicing of exon s, and in charge isomers, generated by posttranslational modifications . Different isoforms and charge isomers presumably subserve different functions, and they vary in abundance in immature myelin found during myelinogenesis and remyelination compared with mature myelin. The 18.5 -kd isomer is most abundant in normal human adults and consequently ha s been used almost exclusively for immunologic studies in MS. In the p resent study, we examined a different but abundant charge isomer of MB P, termed MBP-C8, to determine whether it could be recognized by MBP-s pecific cytotoxic and proliferative T-cell lines (TCL) and whether a T -cell response directed exclusively against citrulline-containing resi dues of MBP-C8 exists in MS patients and healthy controls. We showed t hat citrulline affects antigen recognition by some TCL that are specif ic for areas of MBP that contain the citrulline residues. Following st imulation with MBP-C8, MBP-C8-specific TCL could be generated from bot h MS patients and controls. T-cell responses against antigens that app ear during myelinogenesis and during remyelination may be important in inducing and perpetuating an autoimmune response involved in the path ogenesis of MS.