CITRULLINATED MYELIN BASIC-PROTEIN INDUCES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN LEWIS RATS THROUGH A DIVERSE T-CELL REPERTOIRE

An increased proportion of citrullinated MBP (MBP-C8) occurs in the br ains of multiple sclerosis (MS) patients. In this study, MBP-C8 from g uinea pig (GP) brains was isolated and found encephalitogenic in Lewis rats upon immunization. An encephalitogenic T cell line selected with MBP-C8 preferentially reacted with MBP-C8 over unmodified MBP. This T cell line responded weakly to the dominant encephalitogenic epitope, GP-MBP peptide 70-88, and did not display restricted TCR beta-chain us age (such as V beta 8.2). The distinctive features of MBP-C8 were also demonstrated by its ability to reinduce active EAE in 70% of rats whi ch had recovered from unmodified MBP induced EAE. These findings raise the possibility that citrullinated MBP may elicit a different pathoge nic T cell repertoire for the recurrent phases of inflammatory demyeli nation. (C) 1998 Elsevier Science B.V. All rights reserved.