MHC-restriction, cytokine profile, and immunoregulatory effects of human T cells specific for TCR Vβ CDR2 peptides: Comparison with myelin basic protein-specific T cells

Y. K. Chou, A. D. Weinberg, A. Buenafe, D. N. Bourdette, R. Whitham, J. A.R. Kaleeba, I. F. Robey, D. G. Kavanagh, H. Offner, A. A. Vandenbark

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

HLA-DR2+ patients with multiple sclerosis (MS) that respond to vaccination with TCR Vβ5.2-38-58 peptides have increased frequencies of TCR peptide-specific T cells, reduced frequencies of myelin basic protein (MBP)- specific T cells, and a better clinical course than non-responders. To evaluate possible network regulation of MBP responses by TCR peptide-specific T cells, we compared properties of both cell types. Both MBP- and TCR peptide-specific T cell clones were CD4+ and predominantly HLA-DR restricted. HLA-DR2, which is in linkage disequilibrium in MS patients, preferentially restricted TCR peptide-specific clones as well as MBP-specific responses in HLA-DR2 and DR2,3+ donors. Within the DR2 haplotype, however, both DRβ1*1501 and DRβ5*0101 alleles could restrict T cell responses to Vβ CDR2 peptides, whereas responses to MBP were restricted only by DRβ5*0101. TCR peptide-specific clones expressed message for Th2 cytokines, including IL-4, IL-5, IL-6, IL-10, and TGF-β, whereas MBP-specific T cell clones expressed the Th1 cytokines IFN-γ and IL-2. Consistent with the Th2- like cytokine profile, TCR peptide-specific T cell clones expressed higher levels of CD30 than MBP-specific T cells. Culture supernatants from TCR peptide-specific T cell clones, but not from MBP- or Herpes simplex virus- specific T cells, inhibited both proliferation responses and cytokine message production of MBP-specific T cells. These results demonstrate distinct properties of MBP and TCR peptide-specific T cells, and indicate that both target and bystander Th1 cells can be inhibited by Th2 cytokines secreted by activated TCR peptide-specific T cells. These data support the rationale for TCR peptide vaccination to regulate pathogenic responses mediated by oligoclonal T cells in human autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)838-851
Number of pages14
JournalJournal of Neuroscience Research
Volume45
Issue number6
DOIs
StatePublished - Sep 15 1996

Keywords

  • T cell receptor Vβ chain
  • Th1 cells
  • Th2 cells
  • cytokines
  • multiple sclerosis
  • myelin basic protein (MBP)
  • second complementarity-determining region (CDR2)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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