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Substrate specificity of human ERAP1 haplotypes in vivo identify three functional classes and multiple fine specificity

Substrate specificity of human ERAP1 haplotypes in vivo identify three functional classes and multiple fine specificity
Substrate specificity of human ERAP1 haplotypes in vivo identify three functional classes and multiple fine specificity
Recent genome wide association studies have identified single nucleotide polymorphisms within Endoplasmic Reticulum Aminopeptidase1 (ERAP1) as being associated with autoimmune diseases, cervical carcinoma and hypertension. ERAP1 performs a key final step in antigen processing, trimming N-terminally extended peptides to the final epitope for presentation by MHC I molecules. Here we show that ERAP1 sequenced from individuals is polymorphic, with multiple haplotypes identified. Characterization of the amino acid trimming capacity of the identified haplotypes reveal distinct profiles that correlate with the SNPs they possess. In addition, the properties of the amino acids preferentially trimmed vary between haplotypes. RP-HPLC and mass spectrometry analysis allows classification of the ERAP1 haplotypes into three functional groups; those that have a predominantly i) Normal, ii) Hypo or iii) Hyper-functional activity. These results indicate that the repertoire of peptides presented at the cell surface depends, not only on the MHC I, but also on the ERAP1 expressed within an individual. This therefore has important implications for predisposition to disease, the ability to combat cancer and infection, and also vaccine efficacy.
0022-1767
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
Edwards, Christopher
818e3e0d-4a3d-42a4-a226-38a7c6a4fbed
Elliott, Tim
8e43fe0d-c251-4ee8-80fa-bcffc8c7e153
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
Edwards, Christopher
818e3e0d-4a3d-42a4-a226-38a7c6a4fbed
Elliott, Tim
8e43fe0d-c251-4ee8-80fa-bcffc8c7e153
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4

Reeves, Emma, Edwards, Christopher, Elliott, Tim and James, Edward (2013) Substrate specificity of human ERAP1 haplotypes in vivo identify three functional classes and multiple fine specificity. Journal of Immunology, 190 (S1), [P5034].

Record type: Meeting abstract

Abstract

Recent genome wide association studies have identified single nucleotide polymorphisms within Endoplasmic Reticulum Aminopeptidase1 (ERAP1) as being associated with autoimmune diseases, cervical carcinoma and hypertension. ERAP1 performs a key final step in antigen processing, trimming N-terminally extended peptides to the final epitope for presentation by MHC I molecules. Here we show that ERAP1 sequenced from individuals is polymorphic, with multiple haplotypes identified. Characterization of the amino acid trimming capacity of the identified haplotypes reveal distinct profiles that correlate with the SNPs they possess. In addition, the properties of the amino acids preferentially trimmed vary between haplotypes. RP-HPLC and mass spectrometry analysis allows classification of the ERAP1 haplotypes into three functional groups; those that have a predominantly i) Normal, ii) Hypo or iii) Hyper-functional activity. These results indicate that the repertoire of peptides presented at the cell surface depends, not only on the MHC I, but also on the ERAP1 expressed within an individual. This therefore has important implications for predisposition to disease, the ability to combat cancer and infection, and also vaccine efficacy.

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Published date: 1 May 2013

Identifiers

Local EPrints ID: 443689
URI: http://eprints.soton.ac.uk/id/eprint/443689
ISSN: 0022-1767
PURE UUID: 246d3950-0c61-44ab-a063-d8e59f52dd79
ORCID for Edward James: ORCID iD orcid.org/0000-0001-8638-7928

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Date deposited: 09 Sep 2020 16:30
Last modified: 18 Feb 2021 17:07

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Contributors

Author: Emma Reeves
Author: Christopher Edwards
Author: Tim Elliott
Author: Edward James ORCID iD

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