Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?

Five years ago, we reported the identification and characterization of several regulatory T-cell epitopes (now called Tregitopes) that were discovered in the heavy and light chains of IgG (De Groot et al. Blood, 2008). When added ex vivo to human PBMCs, these Tregitopes activated regulatory T cells...

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Main Authors: Anne S. De Groot, Leslie Cousens, Federico Mingozzi, William Martin
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2013/493138
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author Anne S. De Groot
Leslie Cousens
Federico Mingozzi
William Martin
author_facet Anne S. De Groot
Leslie Cousens
Federico Mingozzi
William Martin
author_sort Anne S. De Groot
collection DOAJ
description Five years ago, we reported the identification and characterization of several regulatory T-cell epitopes (now called Tregitopes) that were discovered in the heavy and light chains of IgG (De Groot et al. Blood, 2008). When added ex vivo to human PBMCs, these Tregitopes activated regulatory T cells (Tregs), increased expression of the transcription factor FoxP3, and induced IL-10 expression in CD4+ T cells. We have now shown that coadministration of the Tregitopes in vivo, in a number of different murine models of autoimmune disease, can suppress immune responses to antigen in an antigen-specific manner, and that this response is mediated by Tregs. In addition we have shown that, although these are generally promiscuous epitopes, the activity of individual Tregitope peptides is restricted by HLA. In this brief report, we provide an overview of the effects of Tregitopes in vivo, discuss potential applications, and suggest that Tregitopes may represent one of the “active pharmaceutical ingredients” of IVIg. Tregitope applications may include any of the autoimmune diseases that are currently treated almost exclusively with intravenous immunoglobulin G (IVIG), such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Multifocal Motor Neuropathy (MMN), as well as gene therapy and allergy where Tregitopes may provide a means of inducing antigen-specific tolerance.
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spelling doaj-art-41e564bf4c2d417b8ba930178eba75c72025-08-20T02:39:16ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/493138493138Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?Anne S. De Groot0Leslie Cousens1Federico Mingozzi2William Martin3Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, USAEpiVax, Inc., 146 Clifford Street, Providence, RI, USAGenethon, Evry, FranceEpiVax, Inc., 146 Clifford Street, Providence, RI, USAFive years ago, we reported the identification and characterization of several regulatory T-cell epitopes (now called Tregitopes) that were discovered in the heavy and light chains of IgG (De Groot et al. Blood, 2008). When added ex vivo to human PBMCs, these Tregitopes activated regulatory T cells (Tregs), increased expression of the transcription factor FoxP3, and induced IL-10 expression in CD4+ T cells. We have now shown that coadministration of the Tregitopes in vivo, in a number of different murine models of autoimmune disease, can suppress immune responses to antigen in an antigen-specific manner, and that this response is mediated by Tregs. In addition we have shown that, although these are generally promiscuous epitopes, the activity of individual Tregitope peptides is restricted by HLA. In this brief report, we provide an overview of the effects of Tregitopes in vivo, discuss potential applications, and suggest that Tregitopes may represent one of the “active pharmaceutical ingredients” of IVIg. Tregitope applications may include any of the autoimmune diseases that are currently treated almost exclusively with intravenous immunoglobulin G (IVIG), such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Multifocal Motor Neuropathy (MMN), as well as gene therapy and allergy where Tregitopes may provide a means of inducing antigen-specific tolerance.http://dx.doi.org/10.1155/2013/493138
spellingShingle Anne S. De Groot
Leslie Cousens
Federico Mingozzi
William Martin
Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?
Clinical and Developmental Immunology
title Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?
title_full Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?
title_fullStr Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?
title_full_unstemmed Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?
title_short Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?
title_sort tregitope peptides the active pharmaceutical ingredient of ivig
url http://dx.doi.org/10.1155/2013/493138
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AT federicomingozzi tregitopepeptidestheactivepharmaceuticalingredientofivig
AT williammartin tregitopepeptidestheactivepharmaceuticalingredientofivig