title: Regulatory T cell epitopes (Tregitopes) in IgG induce tolerance in vivo and lack immunogenicity per se.
abstract: Tregitopes are a set of epitopes, derived from IgG, that bind to MHCII, activate nTregs, and promote tolerance. We have now confirmed that coadministration of Tregitopes with a range of proteins (autoantigens and nominal antigens, such as OVA) in vitro and in vivo leads to suppression of T cell and antibody responses to the test antigens. In this study, we demonstrate that Tregitopes are not immunogenic in vivo even when emulsified with strong adjuvants, such as IFA or CFA. Moreover, in vivo administration of Tregitopes with IFA or CFA does not induce Th1 or Th2 cytokine expression under restimulation conditions in vitro. We investigated tolerance induction by codelivering Tregitopes with OVA using B cells. When B cells were pulsed with OVA plus Tregitopes and transferred into naïve mice, we found that cellular and humoral immune responses to the OVA were suppressed. As a result of their ability to induce Tregs and the absence of immunogenicity in the context of strong adjuvants, Tregitopes might be considered a novel immunomodulatory approach for the suppression of immune responses to protein therapeutics (such as FVIII and mAb), as well as for treatment of autoimmune diseases.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.forename: Robert
authors.initials: R
authors.lastname: Rossi
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007518:Isoantibodies / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D007518:Isoantibodies; C111390:OVA 323-339; D010446:Peptide Fragments; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: IVIg; Treg; immunomodulation