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TitleHLA-A29 does not present immunogenic epitopes of the Retinal S-Antigen in patients with Birdshot Uveitis
PurposeRetinal arrestin (Retinal S-antigen) is widely considered as the candidate autoantigen for Birdshot Uveitis, a severe inflammatory eye condition that only affects HLA-A29-positive individuals.
MethodsWe studied the HLA-A29 immunopeptidome from patient-derived cells engineered to stably express the retinal S-antigen by mass spectrometry.
ResultsAmong peptides presented by HLA-A29, we identified two peptides derived from the retinal S-antigen that were also in vitro substrates of the antigen presentation aminopeptidases ERAP1 and ERAP2 that are genetically implicated in the pathogenesis of Birdshot Uveitis. Multiplexed HLA-A29-peptide dextramer analysis revealed no enrichment for antigen-specific T cells reactive to the identified retinal S-antigen peptides in blood of patients or HLA-A29-positive controls.
ConclusionThese results indicate that the retinal S-antigen is unlikely a primary autoantigen for birdshot uveitis.
Conflict of interestNo
Authors 1
Last nameHIDDINGH
Initials of first name(s)S
DepartmentCTI/Ophthalmology
CityUtrecht
CountryNetherlands
Authors 2
Last nameVenema
Initials of first name(s)WJ
DepartmentCTI/Ophthalmology
CityUtrecht
CountryNetherlands
Authors 3
Last nameClaas
Initials of first name(s)FHJ
DepartmentImmunology
CityLeiden
CountryNetherlands
Authors 4
Last nameMulder
Initials of first name(s)A
DepartmentImmunology
CityLeiden
CountryNetherlands
Authors 5
Last nameJanssen
Initials of first name(s)GMC
DepartmentCenter for Proteomics and Metabolomics
CityLeiden
CountryNetherlands
Authors 6
Last namede Boer
Initials of first name(s)JH
DepartmentOphthalmology
CityUtrecht
CountryNetherlands
Authors 7
Last namevan Veelen
Initials of first name(s)PA
DepartmentCenter for Proteomics and Metabolomics
CityLeiden
CountryNetherlands
Authors 8
Last nameKuiper
Initials of first name(s)JJW
DepartmentOphthalmology/CTI
CityUtrecht
CountryNetherlands