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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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IMMUNOBIOLOGY

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

Anne S. De Groot1,2, Leonard Moise1, Julie A. McMurry1, Erik Wambre3, Laurence Van Overtvelt3, Philippe Moingeon3, David W. Scott4, and William Martin1

1 EpiVax, Providence, RI; 2 University of Rhode Island, Providence; 3 Stallergenes, Anthony, France; and 4 University of Maryland, Baltimore

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+CD25HiFoxP3+ natural regulatory T cells (nTRegs). 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 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 nTRegs that tips the resulting immune response toward tolerance rather than immunogenicity.


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Related Article in Blood Online:

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



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