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 language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology