HLA-A29 does not present immunogenic epitopes of the Retinal S-Antigen in patients with Birdshot Uveitis
Purpose
Retinal 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.
Methods
We studied the HLA-A29 immunopeptidome from patient-derived cells engineered to stably express the retinal S-antigen by mass spectrometry.
Results
Among 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.
Conclusion
These results indicate that the retinal S-antigen is unlikely a primary autoantigen for birdshot uveitis.
Conflict of interest
No
Authors 1
Last name
HIDDINGH
Initials of first name(s)
S
Department
CTI/Ophthalmology
City
Utrecht
Country
Netherlands
Authors 2
Last name
Venema
Initials of first name(s)
WJ
Department
CTI/Ophthalmology
City
Utrecht
Country
Netherlands
Authors 3
Last name
Claas
Initials of first name(s)
FHJ
Department
Immunology
City
Leiden
Country
Netherlands
Authors 4
Last name
Mulder
Initials of first name(s)
A
Department
Immunology
City
Leiden
Country
Netherlands
Authors 5
Last name
Janssen
Initials of first name(s)
GMC
Department
Center for Proteomics and Metabolomics
City
Leiden
Country
Netherlands
Authors 6
Last name
de Boer
Initials of first name(s)
JH
Department
Ophthalmology
City
Utrecht
Country
Netherlands
Authors 7
Last name
van Veelen
Initials of first name(s)
PA
Department
Center for Proteomics and Metabolomics
City
Leiden
Country
Netherlands
Authors 8
Last name
Kuiper
Initials of first name(s)
JJW
Department
Ophthalmology/CTI
City
Utrecht
Country
Netherlands
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