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A restricted T cell response to myelin basic protein (MBP) is stable in multiple sclerosis (MS) patients
A Uccelli1, D Giunti, M Salvetti
1Dipartimento di Scienze Neurologiche e Neuroriabilitazione, Università di Genova, Italy.
Abstract:
The close resemblance of MS to the animal model experimental autoimmune encephalomyelitis (EAE) has provided compelling data sustaining a pathogenic role of circulating T cells reactive against MBP. T cell antigen receptor (TCR) usage in EAE is commonly considered restricted; nevertheless, dynamic changes of TCR usage correlate with the course of EAE, resulting in a limited repertoire during early stages of disease activity followed by the recruitment of other T cells reactive against new determinants. Although a broader TCR repertoire mediates the response to MBP in humans, a restricted intraindividual heterogeneity may occur in some MS patients. In the present study we characterize the response to MBP in MS subjects with relapsing remitting disease from two sampling time points 12 months apart. MBP-specific T cell lines (TCL) were first generated from eight MS individuals and two healthy subjects. New TCL were obtained after 12 months from one control and three MS patients whose response, at the first time point, was directed against a single epitope. Interestingly, these three subjects had a stable and mild disease. Few TCL obtained at two time points from the MS individuals recognized the same immunodominant epitope and shared identical TCR Vbeta sequences. In the control we could not detect a restriction of the repertoire. These findings suggest that in some MS patients with benign disease a predominant T cell response to a single determinant may be detectable at different moments and is mediated by clonally expanded populations.
Insights
In some multiple sclerosis (MS) patients with mild disease, T cell responses to myelin basic protein (MBP) show a restricted T cell receptor (TCR) repertoire. This suggests a stable, dominant T cell response to a single epitope over time.
Area of Science:
- Immunology
- Neuroimmunology
- T cell biology
Background:
- Multiple Sclerosis (MS) shares similarities with experimental autoimmune encephalomyelitis (EAE), suggesting a role for T cells targeting myelin basic protein (MBP).
- T cell receptor (TCR) usage in EAE is dynamic, initially restricted and broadening over time.
- While human MS responses to MBP are generally broader, restricted TCR repertoires may occur in some patients.
Purpose of the Study:
- To characterize the MBP-specific T cell response and TCR usage in relapsing-remitting MS patients over a 12-month period.
- To investigate if a restricted T cell repertoire against MBP is maintained over time in MS patients.
Main Methods:
- Generation of MBP-specific T cell lines (TCL) from eight MS patients and two healthy controls at two time points, 12 months apart.
- Analysis of TCR Vbeta sequences from TCL to assess repertoire diversity.
- Characterization of epitope specificity for MBP-reactive T cells.
Main Results:
- Few MBP-specific TCL from MS patients recognized the same immunodominant epitope and shared identical TCR Vbeta sequences at both time points.
- Three MS patients with stable, mild disease showed a response directed against a single epitope at the initial time point, maintained after 12 months.
- No repertoire restriction was detected in the healthy control subjects.
Conclusions:
- In some MS patients with benign disease, a predominant T cell response to a single MBP determinant can be stable over time.
- This stable response is mediated by clonally expanded T cell populations.
- Findings suggest a potential role for restricted T cell responses in the pathogenesis or course of certain MS patient subgroups.