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Naturally occurring ERAP1 haplotypes encode functionally distinct alleles with fine substrate specificity

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Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims peptides for MHC class I presentation, influencing the degree and specificity of CD8+ T cell responses. Single-nucleotide polymorphisms within the exons encoding ERAP1 are associated with autoimmune diseases and cervical carcinoma, but it is not known whether they act independently or as disease-associated haplotypes. We sequenced ERAP1 from 20 individuals and show that single-nucleotide polymorphisms occur as distinct haplotypes in the human population and that these haplotypes encode functionally distinct ERAP1 alleles. Using a wide range of substrates, we are able to demonstrate that for any given substrate distinct ERAP1 alleles can be “normal,” “hypofunctional,” or “hyperfunctional” and that each allele has a trend bias toward one of these three activities. Thus, the repertoire of peptides presented at the cell surface for recognition by CTL is likely to depend on the precise combination of both MHC class I and ERAP1 alleles expressed within an individual, and has important implications for predisposition to disease.

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Reeves, E., Edwards, C.J., Elliott, T. and James, E. (2013) Naturally occurring ERAP1 haplotypes encode functionally distinct alleles with fine substrate specificity Journal of Immunology, 191, (1), pp. 35-43. (doi:10.4049/jimmunol.1300598). (PMID:23733883).

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e-pub ahead of print date: 3 June 2013
Published date: 1 July 2013
Organisations: Faculty of Medicine


Local EPrints ID: 353202
ISSN: 0022-1767
PURE UUID: 4f92ac17-8ec4-4355-8081-ced5ddb9b2ac
ORCID for T. Elliott: ORCID iD

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Date deposited: 03 Jun 2013 13:21
Last modified: 18 Jul 2017 04:07

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Author: E. Reeves
Author: C.J. Edwards
Author: T. Elliott ORCID iD
Author: E. James

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