Abstract
Defining the epitope specificity of CD8+ T cells is an important goal in autoimmune and immune-mediated disease research. We have developed a translational molecular approach to determine the epitope specificity of CD8+ T cells using the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS). TMEV-specific CD8+ T cells were isolated from brains and spleens of 7-day TMEV-infected C57BL/6J mice and stimulated by Cos-7 cells that were co-transfected with expression vectors encoding the Db class I molecule along with overlapping segments of the TMEV genome. Both brain-infiltrating and spleen-derived CD8+ T cells expressed IFN-γ when Cos-7 cells were co-transfected with Db class I molecule and the TMEV genomic segment that encoded the immunodominant TMEV epitope. This demonstrated that peripheral and brain-infiltrating CD8+ T-cell responses were focused on peptide epitope(s) encoded by the same region of the TMEV genome. We propose that a similar molecular approach could also be used to determine the antigen specificity of suppressor CD8 T cells by the measurement of transforming growth factor-β (TGF-β) production. In addition, with a randomly generated library and peripheral blood or isolated CSF CD8+ T cells, this would be an effective method of predicting the epitope specificity of CD8+ T cells in human inflammatory CNS diseases, in animal models of MS or other organ-specific inflammatory diseases with a protective or pathogenic role of CD8 T cells.
Original language | English (US) |
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Pages (from-to) | 805-810 |
Number of pages | 6 |
Journal | Human Immunology |
Volume | 69 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2008 |
Keywords
- Effector CD8+ T cell
- Epitope
- Genomic library
- Suppressor CD8+ T cell
- Theiler's murine encephalomyelitis virus (TMEV)
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology