Specificity of human T cell clones reactive to immunodominant epitopes of myelin basic protein

Y. K. Chou, P. Henderikx, M. Vainiene, Ruth Whitham, Dennis Bourdette, C. H J Chou, G. Hashim, Halina Offner, Arthur Vandenbark

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Several recently discovered lines of evidence support the involvement of myelin basic protein (BP)-specific T cells in multiple sclerosis (MS). To identify potentially relevant immunodominant T cell epitopes, human BP (Hu-BP)-reactive T cell lines were selected from MS and normal donors and tested for reactivity to cleavage fragments and synthetic peptides of Hu-BP. The MS T cell lines responded to more Hu-BP epitopes than did normal lines, showing biased recognition of the N terminal half of the molecule, and one region in the C terminal half, suggesting increased sensitization to BP. The MS lines also differed from normal lines in their decreased percentage of CD8+ T cells. One hundred nine T cell clones isolated from these lines confirmed the reactivity pattern of the lines but did not reflect the mixed phenotype, since all but three clones tested were CD4+. T cell clones from HLA-DR2 homozygous donors responded to a variety of epitopes, indicating that this molecule was permissive in its ability to restrict T cell responses. Other epitopes, including the immunodominant 149-170 sequence, were restricted by several different major histocompatibility complex (MHC) molecules from both MS and normal donors. T cell receptor (TCR) V gene products could be identified on six of 38 clones tested using monoclonal antibodies. From one HLA-DR2 homozygous donor, four of eight clones utilized Vβ5.2 in response to different BP epitopes, providing initial support for the preferential use of a limited set of V region genes in the human response to BP. Preferential TCR V gene use in MS patients would provide the rationale to regulate selectively BP-reactive T cells through immunity directed at the TCR and thus test for the first time the hypothesis that BP-reactive T cells play a critical role in the pathogenesis of MS.

Original languageEnglish (US)
Pages (from-to)280-290
Number of pages11
JournalJournal of Neuroscience Research
Volume28
Issue number2
StatePublished - 1991

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T-Cell Antigen Receptor Specificity
Immunodominant Epitopes
Myelin Basic Protein
Clone Cells
Multiple Sclerosis
T-Lymphocytes
HLA-DR2 Antigen
Tissue Donors
T-Cell Receptor Genes
Epitopes
Proteins
Cell Line
Peptide Fragments
T-Lymphocyte Epitopes
T-Cell Antigen Receptor
Major Histocompatibility Complex
Immunity
Monoclonal Antibodies
Phenotype

Keywords

  • multiple sclerosis
  • T cell receptor
  • V region genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Specificity of human T cell clones reactive to immunodominant epitopes of myelin basic protein. / Chou, Y. K.; Henderikx, P.; Vainiene, M.; Whitham, Ruth; Bourdette, Dennis; Chou, C. H J; Hashim, G.; Offner, Halina; Vandenbark, Arthur.

In: Journal of Neuroscience Research, Vol. 28, No. 2, 1991, p. 280-290.

Research output: Contribution to journalArticle

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AU - Vainiene, M.

AU - Whitham, Ruth

AU - Bourdette, Dennis

AU - Chou, C. H J

AU - Hashim, G.

AU - Offner, Halina

AU - Vandenbark, Arthur

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