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 Blood, 15 October 2008, Vol. 112, No. 8, pp. 3303-3311.
Prepublished online as a Blood First Edition Paper on July 25, 2008; DOI 10.1182/blood-2008-02-138073.

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Submitted February 12, 2008
Accepted June 14, 2008

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

Anne S. De Groot*, Leonard Moise, Julie A. McMurry, Erik Wambre, Lawrence Van Overtvelt, Philippe Moingeon, David W. Scott, and William Martin

University of Rhode Island, Providence, RI, United States
EpiVax, Inc., Providence, RI, United States
Stallergenes, AntonyCedex, France
University of Maryland School of Medicine, Baltomore, MD, United States

* Corresponding author; email: annied{at}epivax.com.

We have identified at least two highly promiscuous MHC Class II T cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4+ CD25HiFoxP3+ natural regulatory T cells (nTReg). Co-incubation of these regulatory T cell epitopes or "Tregitopes" and antigens with PBMC led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with Tregs 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 nTReg that tip the resulting immune response towards tolerance rather than immunogenicity.


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Tregitopes switch on Tregs
Rachel R. Caspi
Blood 2008 112: 3003-3004. [Full Text] [PDF]



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