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

A. S. De Groot, L. Moise, J. A. McMurry, E. Wambre, L. Van Overtvelt, P. Moingeon, D. W. Scott, W. Martin
2008 Blood  
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 Hi FoxP3 ؉ 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
more » ... ssociated 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.
doi:10.1182/blood-2008-02-138073 pmid:18660382 pmcid:PMC2569179 fatcat:lkwgtvq3yjgkjldoswcakrczf4