Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes"

Authors

Anne S. De Groot, University of Rhode IslandFollow
Leonard Moise, University of Rhode IslandFollow
Julie A. McMurry
Erik Wambre
Laurence Van Overtvelt
Philippe Moingeon
David W. Scott
William Martin

Document Type

Article

Date of Original Version

2008

Abstract

We have identified at least 2 highly promiscuous major histocompatibility complex class II T-cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4⁺CD25_HiFoxP3⁺ natural regulatory T cells (nT_Regs). Coincubation of these regulatory T-cell epitopes or “Tregitopes” and antigens with peripheral blood mononuclear cells led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with T_Regs such as FoxP3. In vivo administration of the murine homologue of the Fc region Tregitope resulted in suppression of immune response to a known immunogen. These data suggest that one mechanism for the immunosuppressive activity of IgG, such as with IVIG, may be related to the activity of regulatory T cells. In this model, regulatory T-cell epitopes in IgG activate a subset of nT_Regs that tips the resulting immune response toward tolerance rather than immunogenicity.

Citation/Publisher Attribution

De Groot, A. S., Moise, L., McMurry, J. A., Wambre, E., Van Overtvelt, L., Moingeon, P., Scott, D. W., & Martin, W. (2015). Activation of natural regulatory T cells by IgG Fc-derived peptide 'Tregitopes'. Blood, 112(8), 3303-3311.

Available at: http://www.bloodjournal.org/content/112/8/3303