Complementarity-determining region 3 spectratyping analysis of the TCR repertoire in multiple sclerosis.
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.
Matsumoto
Yoh
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan. matyoh@tmin.ac.jp
Yoon
Wong Kee
WK
Jee
Youngheun
Y
Fujihara
Kazuo
K
Misu
Tatsuro
T
Sato
Shigeru
S
Nakashima
Ichiro
I
Itoyama
Yasuto
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000302:isolation & purification*; D003430:Cross-Sectional Studies; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification*; D016415:Sequence Alignment
D022801:Complementarity Determining Regions; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; C113248:T cell receptor peptide Vbeta5.2