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Review
. 2013 Jan;33 Suppl 1(Suppl 1):S43-9.
doi: 10.1007/s10875-012-9762-4. Epub 2012 Sep 2.

In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity

Leslie P Cousens  1 , Nader Najafian, Federico Mingozzi, Wassim Elyaman, Bruce Mazer, Leonard Moise, Timothy J Messitt, Yan Su, Mohamed Sayegh, Katherine High, Samia J Khoury, David W Scott, Anne S De Groot
Affiliations
Review

In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity

Leslie P Cousens et al. J Clin Immunol. 2013 Jan.

Abstract

Tregitopes are regulatory T cell epitopes derived from immunoglobulin G (IgG) that stimulate CD25(+) FoxP3(+) T cells to expand. In conjunction with these Tregs, Tregitopes can prevent, treat, and even cure autoimmune disease in mouse models, suppress allo-specific responses in murine transplant models, inhibit CD8(+) T cell responses to recombinant adeno-associated virus (AAV) gene transfer vectors, and induce adaptive Tregs in DO11.10 mice. In this review of recent Tregitope studies, we summarize their effects in vitro and describe recent comparisons between intravenous IgG (IVIG) and Tregitopes in standard in vivo immune tolerance models. Further investigations of the mechanism of action of Tregitopes in the preclinical models described here will lead to clinical trials where Tregitopes may have the potential to alter the treatment of autoimmune disease, transplantation, and allergy, and to improve the efficiency of gene and protein replacement therapies.

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Conflict of interest statement

Drs Najafian, Mingozzi, Elyaman, Mazer, High, Khoury, Scott, and Su are current consultants/collaborators of EpiVax, Inc., the company that discovered Tregitopes and where the IP is held.

Figures

Fig. 1
Fig. 1
Tregitopes are highly conserved Treg epitopes found in IgG. They are postulated to reduce the immunogenicity of neo-epitopes in the hypervariable region of IgG CDR. De Groot AS, Moise L, McMurry JA, Wambre E, Van Overtvelt L, Moingeon P, et al. Activation of natural regulatory T cells by IgG Fc-derived peptide “Tregitopes.” Blood. 2008; 112(8):3303–11. American Society of Hematology, Copyright 2012. Reproduced with permission of American Society of Hematology (ASH)
Fig. 2
Fig. 2
Proposed Tregitope mechanism of action. The following step-by-step sequence of events may lead to nTreg activation, antigen-presenting cell (APC) modulation, and either suppression of T effectors or induction of iTregs in the presence of Tregitopes: (Step 1) Tregitopes are presented by activated APC to Tregs that have Tregitope-specific TCR. These nTregs then either indirectly through cytokine release (Step 2), or directly suppress the activation of (Step 3) antigen-presenting cells (macrophages, B cells, dendritic cells, or others), resulting in downregulation of the co-stimulatory signaling molecules CD80, CD86, and MHC class II. The cytokines released by the nTregs either directly affect (Steps 4 and 5) the functioning of CD4 effector T cells, CD8 T cells, and Th17 T cells; or indirectly regulate (Step 3) these cells through APC or direct cell-to-cell contact. Adapted from [2]
See this image and copyright information in PMC

References

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