Reversal of type 1 diabetes by a new MHC II-peptide chimera: "Single-epitope-mediated suppression" to stabilize a polyclonal autoimmune T-cell process

Marvin Lin, Cristina Stoica-Nazarov, Jacqueline Surls, Margaret Kehl, Constantin Bona, Cara Olsen, Teodor D. Brumeanu, Sofia Casares

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Polyclonality of self-reactive CD4+ T cells is the hallmark of several autoimmune diseases like type 1 diabetes. We have previously reported that a soluble dimeric MHC II-peptide chimera prevents and reverses type 1 diabetes induced by a monoclonal diabetogenic T-cell population in double Tg mice [Casares, S. et al., Nat. Immunol. 2002. 3: 383-391]. Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4+ T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65 217-230-specific CD4+ T cells) using a soluble I-A αβg7/GAD65217-230/Fcγ2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. Activated GAD65217-230-specific T cells and a fraction of the diabetogenic (B9-23-specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. More importantly, this led to the reversal of hyperglycemia for more than 2 months post-therapy in 80% of mice in the context of stabilization of pancreatic insulitis and improved insulin secretion by the β cells. These findings argue for the stabilization of a polyclonal self-reactive T-cell process by a single epitope-mediated bystander suppression. Dimeric MHC class II-peptide chimeras-like approach may provide rational grounds for the development of more efficient antigen-specific therapies in type 1 diabetes.

Original languageEnglish
Pages (from-to)2277-2288
Number of pages12
JournalEuropean Journal of Immunology
Issue number8
StatePublished - Aug 2010
Externally publishedYes


  • Antigen-specific therapy
  • MHC II-peptide chimeras
  • Single epitope-mediated suppression
  • Type 1 diabetes reversal


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