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Citrullinated myelin basic protein induces experimental autoimmune encephalomyelitis in Lewis rats through a diverse
1Department of Neurology, University of Alabama at Birmingham, 35294-0007, USA.
Abstract:
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.
Insights
Citrullinated myelin basic protein (MBP-C8) is elevated in multiple sclerosis (MS) brains. This modified protein can trigger experimental autoimmune encephalomyelitis (EAE) and may drive recurrent inflammatory demyelination.
Area of Science:
- Neuroimmunology
- Protein Chemistry
Background:
- Elevated levels of citrullinated myelin basic protein (MBP-C8) are observed in the brains of multiple sclerosis (MS) patients.
- The role of citrullinated proteins in the pathogenesis of MS remains incompletely understood.
Purpose of the Study:
- To investigate the encephalitogenic potential of citrullinated myelin basic protein (MBP-C8).
- To characterize the T cell response to MBP-C8 in the context of experimental autoimmune encephalomyelitis (EAE).
Main Methods:
- Isolation and characterization of guinea pig MBP-C8.
- Induction of EAE in Lewis rats using MBP-C8.
- Selection and analysis of MBP-C8-specific T cell lines.
- Assessment of T cell reactivity to MBP-C8 versus unmodified MBP.
- Evaluation of MBP-C8's ability to reinduce EAE in recovered rats.
Main Results:
- Isolated MBP-C8 was encephalitogenic in Lewis rats.
- An MBP-C8-selected T cell line showed preferential reactivity to MBP-C8 over unmodified MBP.
- This T cell line responded weakly to the known dominant epitope GP-MBP peptide 70-88 and did not exhibit restricted TCR beta-chain usage.
- MBP-C8 reinduced active EAE in 70% of rats that had recovered from EAE induced by unmodified MBP.
Conclusions:
- Citrullinated MBP (MBP-C8) possesses distinct encephalitogenic properties.
- MBP-C8 may elicit a unique pathogenic T cell repertoire, potentially contributing to recurrent inflammatory demyelination in MS.