The Mechanism of Action of Antigen Processing Independent T Cell Epitopes Designed for Immunotherapy of Autoimmune Diseases

Ella R Shepard; Anja Wegner; Elaine V Hill; Bronwen R Burton; Sarah Aerts; Evelien Schurgers; Brecht Hoedemaekers; Sky T H Ng; Heather B Streeter; Lotta Jansson; David C Wraith

doi:10.3389/fimmu.2021.654201

The Mechanism of Action of Antigen Processing Independent T Cell Epitopes Designed for Immunotherapy of Autoimmune Diseases

Ella R Shepard, Anja Wegner, Elaine V Hill, Bronwen R Burton, Sarah Aerts, Evelien Schurgers, Brecht Hoedemaekers, Sky T H Ng, Heather B Streeter, Lotta Jansson, David C Wraith

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

182 Downloads (Pure)

Abstract

Immunotherapy with antigen-processing independent T cell epitopes (apitopes) targeting autoreactive CD4+ T cells has translated to the clinic and been shown to modulate progression of both Graves' disease and multiple sclerosis. The model apitope (Ac1-9[4Y]) renders antigen-specific T cells anergic while repeated administration induces both Tr1 and Foxp3+ regulatory cells. Here we address why CD4+ T cell epitopes should be designed as apitopes to induce tolerance and define the antigen presenting cells that they target in vivo. Furthermore, we reveal the impact of treatment with apitopes on CD4+ T cell signaling, the generation of IL-10-secreting regulatory cells and the systemic migration of these cells. Taken together these findings reveal how apitopes induce tolerance and thereby mediate antigen-specific immunotherapy of autoimmune diseases.

Original language	English
Article number	654201
Journal	Frontiers in immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.654201
Publication status	Published - 14 Apr 2021

Bibliographical note

Keywords

Tr1 cell
apitope
autoimmune disease
dendritic cell
immunological tolerance
immunotherapy
interleukin-10
synthetic peptide

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3389/fimmu.2021.654201Licence: Creative Commons: Attribution (CC BY)

fimmu-12-654201Final published version, 2.42 MBLicence: Creative Commons: Attribution (CC BY)

T-cell epitopes for antigen-specific immunotherapy of primary biliary cirrhosis
Wraith, D. (Principal Investigator)
Wellcome Trust
1/06/17 → 30/11/18
Project: Research

Cite this

Shepard, E. R., Wegner, A., Hill, E. V., Burton, B. R., Aerts, S., Schurgers, E., Hoedemaekers, B., Ng, S. T. H., Streeter, H. B., Jansson, L., & Wraith, D. C. (2021). The Mechanism of Action of Antigen Processing Independent T Cell Epitopes Designed for Immunotherapy of Autoimmune Diseases. Frontiers in immunology, 12, Article 654201. https://doi.org/10.3389/fimmu.2021.654201

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abstract = "Immunotherapy with antigen-processing independent T cell epitopes (apitopes) targeting autoreactive CD4+ T cells has translated to the clinic and been shown to modulate progression of both Graves' disease and multiple sclerosis. The model apitope (Ac1-9[4Y]) renders antigen-specific T cells anergic while repeated administration induces both Tr1 and Foxp3+ regulatory cells. Here we address why CD4+ T cell epitopes should be designed as apitopes to induce tolerance and define the antigen presenting cells that they target in vivo. Furthermore, we reveal the impact of treatment with apitopes on CD4+ T cell signaling, the generation of IL-10-secreting regulatory cells and the systemic migration of these cells. Taken together these findings reveal how apitopes induce tolerance and thereby mediate antigen-specific immunotherapy of autoimmune diseases.",

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AU - Jansson, Lotta

AU - Wraith, David C

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AB - Immunotherapy with antigen-processing independent T cell epitopes (apitopes) targeting autoreactive CD4+ T cells has translated to the clinic and been shown to modulate progression of both Graves' disease and multiple sclerosis. The model apitope (Ac1-9[4Y]) renders antigen-specific T cells anergic while repeated administration induces both Tr1 and Foxp3+ regulatory cells. Here we address why CD4+ T cell epitopes should be designed as apitopes to induce tolerance and define the antigen presenting cells that they target in vivo. Furthermore, we reveal the impact of treatment with apitopes on CD4+ T cell signaling, the generation of IL-10-secreting regulatory cells and the systemic migration of these cells. Taken together these findings reveal how apitopes induce tolerance and thereby mediate antigen-specific immunotherapy of autoimmune diseases.

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The Mechanism of Action of Antigen Processing Independent T Cell Epitopes Designed for Immunotherapy of Autoimmune Diseases

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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Projects

T-cell epitopes for antigen-specific immunotherapy of primary biliary cirrhosis

Cite this