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Characterization of the Antigen Specificity and TCR Repertoire, and TCR-Based DNA Vaccine Therapy in Myelin Basic Protein-Induced Autoimmune Encephalomyelitis in DA Rats
- Source :
- The Journal of Immunology. 170:6371-6378
- Publication Year :
- 2003
- Publisher :
- The American Association of Immunologists, 2003.
-
Abstract
- Like Lewis rats, DA rats are an experimental autoimmune encephalomyelitis (EAE)-susceptible strain and develop severe EAE upon immunization with myelin basic protein (MBP). However, there are several differences between the two strains. In the present study we induced acute EAE in DA rats by immunization with MBP and MBP peptides and examined the Ag specificity and TCR repertoire of encephalitogenic T cells. It was found that although immunization with MBP and a peptide corresponding to its 62–75 sequence (MBP62–75) induced clinical EAE, the responses of lymph node T cells isolated from MBP-immunized rats to MBP62–75 was marginal, indicating that this peptide contains major encephalitogenic, but not immunodominant, epitopes. The TCR analysis by CDR3 spectratyping of spinal cord T cells revealed that Vβ10 and Vβ15 spectratype expansion was always found in MBP62–75-immunized symptomatic rats. On the basis of these findings, we examined the encephalitogenicity of Vβ10- and Vβ15-positive T cells. First, the adoptive transfer experiments revealed that Vβ10-positive T line cells derived from MBP62–75-immunized rats induced clinical EAE in recipients. Second, administration of DNA vaccines encoding Vβ10 and Vβ15, alone or in combination, ameliorated MBP62–75-induced EAE. Collectively, it was strongly suggested that Vβ10- and Vβ15-positive T cells are encephalitogenic. Analyses of the Ag specificity and T cell repertoire of pathogenic T cells performed in this study provide useful information for designing specific immunotherapies against autoimmune diseases.
- Subjects :
- Adoptive cell transfer
Encephalomyelitis, Autoimmune, Experimental
Injections, Subcutaneous
Receptors, Antigen, T-Cell, alpha-beta
T cell
Encephalomyelitis
Guinea Pigs
Molecular Sequence Data
Immunology
Epitopes, T-Lymphocyte
Biology
Polymerase Chain Reaction
Epitope
Cell Line
Species Specificity
Antigen
T-Lymphocyte Subsets
Vaccines, DNA
medicine
Animals
Immunology and Allergy
Amino Acid Sequence
Experimental autoimmune encephalomyelitis
T-cell receptor
Myelin Basic Protein
Rats, Inbred Strains
Sequence Analysis, DNA
medicine.disease
Adoptive Transfer
Complementarity Determining Regions
Peptide Fragments
Rats
Myelin basic protein
medicine.anatomical_structure
biology.protein
Disease Susceptibility
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 170
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....9f6f9b044efb2fe16f44db9d17877497