Complementarity-determining region 3 spectratyping analysis of the TCR repertoire in multiple sclerosis

Yoh Matsumoto, Wong Kee Yoon, Youngheun Jee, Kazuo Fujihara, Tatsuro Misu, Shigeru Sato, Ichiro Nakashima, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

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 Vβ5.2 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 Vβ5.2 expansion was detectable in the majority of patients examined. These findings suggest that Vβ5.2 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.

Original languageEnglish
Pages (from-to)4846-4853
Number of pages8
JournalJournal of Immunology
Volume170
Issue number9
DOIs
Publication statusPublished - 2003 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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