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Complementarity-determining region 3 spectratyping analysis of the TCR repertoire in multiple sclerosis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 May 01; Vol. 170 (9), pp. 4846-53. - Publication Year :
- 2003
-
Abstract
- Multiple sclerosis (MS) is considered to be an autoimmune disease mediated by T cells reactive with Ags in the CNS. Therefore, it has been postulated that neuroantigen-reactive T cells bearing particular types of TCRs are expanded clonally during the course of the disease. However, there is a controversy with regard to the TCR usage by T cells associated with the development of MS. By the use of complementarity-determining region 3 spectratyping analysis that is shown to be a useful tool for identification of pathogenic TCR in autoimmune disease models, we tried to demonstrate that spectratype was T cells bearing particular types of TCR are activated in MS patients. Consequently, it was found that Vbeta5.2 were often oligoclonally expanded in peripheral blood of MS patients, but not of healthy subjects. Sequence analysis of the complementarity-determining region 3 region of spectratype-derived TCR clones revealed that the predominant TCR clone was different from patient to patient, but that similar results were obtained in a patient examined at different time points. More importantly, examination of cerebrospinal fluid T cells and longitudinal studies of PBLs from selected patients revealed that Vbeta5.2 expansion was detectable in the majority of patients examined. These findings suggest that Vbeta5.2 spectratype expansion is associated with the development of MS and that TCR-based immunotherapy can be applicable to MS patients if the TCR activation pattern of each patient is determined at different stages of the disease.
- Subjects :
- Adolescent
Adult
Aged
Alleles
Amino Acid Sequence
Cloning, Molecular
Complementarity Determining Regions blood
Complementarity Determining Regions cerebrospinal fluid
Cross-Sectional Studies
Female
HLA-DR Antigens blood
HLA-DR Antigens genetics
HLA-DRB1 Chains
Histocompatibility Testing methods
Humans
Longitudinal Studies
Lymphocyte Subsets chemistry
Lymphocyte Subsets immunology
Male
Middle Aged
Molecular Sequence Data
Multiple Sclerosis blood
Multiple Sclerosis cerebrospinal fluid
Multiple Sclerosis, Chronic Progressive blood
Multiple Sclerosis, Chronic Progressive cerebrospinal fluid
Multiple Sclerosis, Chronic Progressive genetics
Multiple Sclerosis, Chronic Progressive immunology
Multiple Sclerosis, Relapsing-Remitting blood
Multiple Sclerosis, Relapsing-Remitting cerebrospinal fluid
Multiple Sclerosis, Relapsing-Remitting genetics
Multiple Sclerosis, Relapsing-Remitting immunology
Polymerase Chain Reaction methods
Receptors, Antigen, T-Cell, alpha-beta blood
Sequence Alignment
Complementarity Determining Regions genetics
Complementarity Determining Regions isolation & purification
Multiple Sclerosis genetics
Multiple Sclerosis immunology
Receptors, Antigen, T-Cell, alpha-beta genetics
Receptors, Antigen, T-Cell, alpha-beta isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 170
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12707368
- Full Text :
- https://doi.org/10.4049/jimmunol.170.9.4846