The University of Southampton
University of Southampton Institutional Repository

Functionally distinct ERAP1 allotype combinations distinguish individuals with Ankylosing Spondylitis

Record type: Article

For more than 40 y, expression of HLA-B27 has been strongly associated with the chronic inflammatory disease Ankylosing Spondylitis (AS); however, the mechanisms underlying this association are still unknown. Single nucleotide polymorphisms within the aminopeptidase endoplasmic reticulum aminopeptidase 1 (ERAP1), which is essential for trimming peptides before they are presented to T cells by major histocompatibility complex (MHC) class I molecules, have been linked with disease. We show that ERAP1 is a highly polymorphic molecule comprising allotypes of single nucleotide polymorphisms. The prevalence of specific ERAP1 allotypes is different between AS cases and controls. Both chromosomal copies of ERAP1 are codominantly expressed, and analysis of allotype pairs provided clear stratification of individuals with AS versus controls. Functional analyses demonstrated that ERAP1 allotype pairs seen in AS cases were poor at generating optimal peptide ligands for binding to murine H-2K(b) and -D(b) and the AS-associated HLA-B*2705. We therefore provide strong evidence that polymorphic ERAP1 alters protein function predisposing an individual to AS via its influence on the antigen processing pathway.

Full text not available from this repository.

Citation

Reeves, Emma, Colebatch-Bourn, Alexandra, Elliott, Tim, Edwards, Christopher J. and James, Edward (2014) Functionally distinct ERAP1 allotype combinations distinguish individuals with Ankylosing Spondylitis Proceedings of the National Academy of Sciences, 111, (49), pp. 17594-17599. (doi:10.1073/pnas.1408882111). (PMID:25422414).

More information

Accepted/In Press date: 5 November 2014
e-pub ahead of print date: 24 November 2014
Published date: 9 December 2014
Keywords: ankylosing spondylitis, ERAP1, HLA-B27, antigen presentation, antigen processing
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 380413
URI: http://eprints.soton.ac.uk/id/eprint/380413
ISSN: 0027-8424
PURE UUID: e9af079b-2111-4b0f-a33f-ee87452a624f
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 14 Sep 2015 12:54
Last modified: 17 Jul 2017 20:35

Export record

Altmetrics

Contributors

Author: Emma Reeves
Author: Alexandra Colebatch-Bourn
Author: Tim Elliott ORCID iD
Author: Edward James

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×