title: Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes".
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(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 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.
authors.affiliation: EpiVax, Providence, RI, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.forename: Julie A
authors.initials: JA
authors.lastname: McMurry
authors.forename: Erik
authors.initials: E
authors.lastname: Wambre
authors.forename: Laurence
authors.initials: L
authors.lastname: Van Overtvelt
authors.forename: Philippe
authors.initials: P
authors.lastname: Moingeon
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.forename: William
authors.initials: W
authors.lastname: Martin
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008925:Mites; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents