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 brains of multiple sclerosis (MS) patients. In this study, MBP-C8 from guinea 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 usage (such as Vbeta88.2). The distinctive features of MBP-C8 were also demonstrated by its ability to reinduce active EAE in 70% of rats which had recovered from unmodified MBP induced EAE. These findings raise the possibility that citrullinated MBP may elicit a different pathogenic T cell repertoire for the recurrent phases of inflammatory demyelination.
Department of Neurology, University of Alabama at Birmingham, 35294-0007, USA.
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D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D002956:Citrulline / Q000378:metabolism*; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006168:Guinea Pigs; D007120:Immunochemistry; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic
D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C113782:myelin basic protein 70-88; D002956:Citrulline