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Fine T cell receptor repertoire analysis of spinal cord T cells responding to the major and minor epitopes of myelin basic protein during rat autoimmune encephalomyelitis
- Source :
- Journal of neuroscience research. 59(1)
- Publication Year :
- 2000
-
Abstract
- Experimental autoimmune encephalomyelitis is a disease induced by neuroantigen-reactive T cells bearing particular types of T cell receptor (TCR). Although the nature of TCRs of encephalitogenic T cells has been partially delineated using encephalitogenic T cell clones established in vitro, the entire TCR repertoire formed in situ after immunization with neuroantigen remains unclear. In the present study, we immunized Lewis rats with myelin basic protein (MBP) and its fragment peptides and determined the TCR repertoire of spinal cord T cells formed after the immunization by CDR3 spectra-typing. It was revealed that the oligoclonal expansion of Vbeta2, Vbeta8.2, and Vbeta17 spectratypes was detectable after immunization with guinea pig MBP and its immunodominant epitope, the 68-88 sequence, whereas immunization with a peptide containing a minor epitope induced Vbeta10 expansion. Immunization with rat MBP induced much broader TCR Vbeta expansion (all of the above Vbetas plus Vbeta3). These findings suggest that TCRs activated by immunization with guinea pig MBP used as heteroclitic immunogen recognize autoantigen, rat MBP. Furthermore, the strategy used in this study gives insight into the pathogenesis of autoimmune disease and provides useful information for designing TCR-based immunotherapy.
- Subjects :
- Immunogen
Encephalomyelitis, Autoimmune, Experimental
medicine.medical_treatment
T cell
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
Immunoglobulin Variable Region
Receptors, Antigen, T-Cell
chemical and pharmacologic phenomena
Biology
Epitope
Cellular and Molecular Neuroscience
Epitopes
medicine
Animals
Experimental autoimmune encephalomyelitis
T-cell receptor
hemic and immune systems
Myelin Basic Protein
Rats, Inbred Strains
Immunotherapy
medicine.disease
Complementarity Determining Regions
Myelin basic protein
Rats
medicine.anatomical_structure
Immunization
Spinal Cord
Immunology
biology.protein
Subjects
Details
- ISSN :
- 03604012
- Volume :
- 59
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of neuroscience research
- Accession number :
- edsair.doi.dedup.....fb06ba35d622474631c8855ab3fb0f6b