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CD4 T-cell epitopes of human alpha B-crystallin
Yuan K Chou1, Gregory G Burrows, Dorian LaTocha
1Department of Neurology, Oregon Health and Science University, Portland, Oregon 97201, USA. chouy@ohsu.edu
Journal of Neuroscience Research
|January 27, 2004
Summary
Oligodendroglial alpha B-crystallin, a protein in early multiple sclerosis (MS) lesions, triggers autoreactive T-cells. These T-cells (Th1) may contribute to MS pathogenesis by targeting specific alpha B-crystallin peptides.
Area of Science:
- Neuroimmunology
- Molecular Medicine
- Autoimmunity
Background:
- Oligodendroglial alpha B-crystallin is present in early multiple sclerosis (MS) lesions.
- Alpha B-crystallin is associated with the myelin sheath, a key component affected in MS.
Purpose of the Study:
- To investigate the role of alpha B-crystallin-specific T-cells in multiple sclerosis (MS).
- To identify specific T-cell epitopes of alpha B-crystallin in MS patients.
Main Methods:
- Selected T-cell lines specific for human alpha B-crystallin from peripheral blood mononuclear cells (PBMC) of HLA-DR2 homozygous MS patients.
- Determined CD4 T-cell epitopes by assessing T-cell proliferation to synthetic overlapping peptides of alpha B-crystallin.
- Analyzed cytokine profiles (IL-2, IFN-gamma, TNF-alpha) and HLA-DR2 binding motifs.
Main Results:
- Alpha B-crystallin-specific T-cells were CD4+ and restricted by HLA-DRB1*1501, expressing Th1 cytokines.
- T-cell lines proliferated significantly to alpha B-crystallin peptides 21-40, 41-60, and 131-150.
- PBMC from early active MS patients showed stronger proliferation to epitope-containing peptides compared to later stage MS patients or healthy controls.
Conclusions:
- Autoreactive alpha B-crystallin-specific Th1 cells are identified in MS patients.
- These T-cells target specific alpha B-crystallin epitopes, suggesting a potential role in MS pathogenesis.
- Alpha B-crystallin-specific T-cell responses may contribute to the development and progression of multiple sclerosis.