TCR peptide vaccination induced TH2 immune regulation in multiple sclerosis

A. A. Vandenbark, Y. K. Chou, R. Whitham, A. Buenafe, D. Liefeid, D. Cavanagh, S. Cooper, G. A. Hashim, H. Offner, D. Bourdette

Research output: Contribution to journalArticle

Abstract

Oligoclonal Thl responses to neuroantigens such as myelin basic protein (MBP) may contribute to the pathogenesis of MS, raising the possibility of TCR peptide vaccines to induce anti-idiotypic regulation. Twenty-three patients with progressive MS were treated for 12 months with native VB5.2 CDR2 peptide, a cross-reactive Y49T-substituted VB5.2 CDR2 peptide, or placebo, and evaluated in a double-blinded fashion for clinical and immunological changes. Patients had more frequent and stronger T cell response to the substituted versus native VB5.2 CDR2 peptide, and response to either peptide was significantly associated with clinical benefit and decreased T cell response to MBP. T cell clones recognizing the VB5.2 peptide were predominantly HLA-DR restricted Th2 cells that inhibited activation of Thl cells specific for MBP by releasing locally suppressive lymphokines, predominantly IL-10, that may affect both the initiating and bystander Thl specificities. These results suggest a therapeutic potential for altered peptides that cross-react with TCR sequences involved in recognition of autoantigens.

Original languageEnglish (US)
Pages (from-to)A1161
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Vandenbark, A. A., Chou, Y. K., Whitham, R., Buenafe, A., Liefeid, D., Cavanagh, D., Cooper, S., Hashim, G. A., Offner, H., & Bourdette, D. (1996). TCR peptide vaccination induced TH2 immune regulation in multiple sclerosis. FASEB Journal, 10(6), A1161.