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ERAP1: a potential therapeutic target for a myriad of diseases

ERAP1: a potential therapeutic target for a myriad of diseases
ERAP1: a potential therapeutic target for a myriad of diseases
Introduction: Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a key regulator of the peptide repertoire displayed by Major Histocompatibility Complex I (MHC I) to circulating CD8 + T cells and NK cells. Studies have highlighted the essential requirement for the generation of stable peptide MHC I in regulating both innate and adaptive immune responses in health and disease.

Areas covered: We review the role of ERAP1 in peptide trimming of N-terminally extended precursors that enter the ER, before loading on to MHC I, and the consequence of loss or downregulation of this activity. Polymorphisms in ERAP1 form multiple combinations (allotypes) within the population, and we discuss the contribution of this ERAP1 variation, and expression, on disease pathogenesis, including the resulting effect on both innate and adaptive immunity. We consider the current efforts to design inhibitors based on approaches using rational design and small molecule screening, and the potential effect of pharmacological modulation on the treatment of autoimmunity and cancer.

Expert opinion: ERAP1 is fundamental for the regulation of immune responses, through generation of the presented peptide repertoire at the cell surface. Modulation of ERAP1 function, through design of inhibitors, may serve as a vital tool for changing immune responses in disease.
CD8+ T cells, ERAP1, MHC I, NK cells, antigen processing and presentation, autoimmunity, cancer
1472-8222
535-544
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
Islam, Yasmin
94082711-bcee-4157-8f67-360d01f81dd5
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
Islam, Yasmin
94082711-bcee-4157-8f67-360d01f81dd5

James, Edward, Reeves, Emma and Islam, Yasmin (2020) ERAP1: a potential therapeutic target for a myriad of diseases. Expert Opinion on Therapeutic Targets, 24 (6), 535-544. (doi:10.1080/14728222.2020.1751821).

Record type: Review

Abstract

Introduction: Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a key regulator of the peptide repertoire displayed by Major Histocompatibility Complex I (MHC I) to circulating CD8 + T cells and NK cells. Studies have highlighted the essential requirement for the generation of stable peptide MHC I in regulating both innate and adaptive immune responses in health and disease.

Areas covered: We review the role of ERAP1 in peptide trimming of N-terminally extended precursors that enter the ER, before loading on to MHC I, and the consequence of loss or downregulation of this activity. Polymorphisms in ERAP1 form multiple combinations (allotypes) within the population, and we discuss the contribution of this ERAP1 variation, and expression, on disease pathogenesis, including the resulting effect on both innate and adaptive immunity. We consider the current efforts to design inhibitors based on approaches using rational design and small molecule screening, and the potential effect of pharmacological modulation on the treatment of autoimmunity and cancer.

Expert opinion: ERAP1 is fundamental for the regulation of immune responses, through generation of the presented peptide repertoire at the cell surface. Modulation of ERAP1 function, through design of inhibitors, may serve as a vital tool for changing immune responses in disease.

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ERAP1 therapeutic target Review - Accepted Manuscript
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Accepted/In Press date: 1 April 2020
e-pub ahead of print date: 4 April 2020
Published date: 2 June 2020
Additional Information: Funding Information: This paper was not funded; however, E Reeves is supported by Cancer Research UK Programme Grant A16997. Publisher Copyright: © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Keywords: CD8+ T cells, ERAP1, MHC I, NK cells, antigen processing and presentation, autoimmunity, cancer

Identifiers

Local EPrints ID: 439631
URI: http://eprints.soton.ac.uk/id/eprint/439631
ISSN: 1472-8222
PURE UUID: 4d5964d9-0647-454c-ae61-0e1ec16cb5f8
ORCID for Edward James: ORCID iD orcid.org/0000-0001-8638-7928

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Date deposited: 28 Apr 2020 16:35
Last modified: 17 Mar 2024 05:30

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Contributors

Author: Edward James ORCID iD
Author: Emma Reeves
Author: Yasmin Islam

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