Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis
Copyright © 2022. Published by Elsevier Inc.
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 247(2023) vom: 25. Feb., Seite 109219 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2023
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't HLA-A29 antigen Arrestin HLA-A Antigens Peptides Autoantigens ERAP1 protein, human EC 3.4.11.- Aminopeptidases plus... |
| Résumé: | Copyright © 2022. Published by Elsevier Inc. BACKGROUND: HLA-A29-positive birdshot chorioretinitis (BCR) is an inflammatory eye disorder that is generally assumed to be caused by an autoimmune response to HLA-A29-presented peptides from retinal arrestin (SAG), yet the epitopes recognized by CD8+ T cells from patients remain to be identified OBJECTIVES: The identification of natural ligands of SAG presented by HLA-A29. To quantify CD8+ T cells reactive to antigenic SAG peptides presented by HLA-A29 in patients and controls METHODS: We performed mass-spectrometry based immunopeptidomics of HLA-A29 of antigen-presenting cell lines from patients engineered to express SAG. MHC-I Dextramer technology was utilised to determine expansion of antigen-specific CD8+ T cells reactive to SAG peptides in complex with HLA-A29 in a cohort of BCR patients, HLA-A29-positive controls, and HLA-A29-negative controls RESULTS: We report on the naturally presented antigenic SAG peptides identified by sequencing the HLA-A29 immunopeptidome of antigen-presenting cells of patients. We show that the N-terminally extended SAG peptide precursors can be trimmed in vitro by the antigen-processing aminopeptidases ERAP1 and ERAP2. Unexpectedly, no enhanced antigen engagement by CD8+ T cells upon stimulation with SAG peptides was observed in patients or HLA-A29-positive controls. Multiplexed HLA-A29-peptide dextramer profiling of a case-control cohort revealed that CD8+ T cells specific for these SAG peptides were neither detectable in peripheral blood nor in eye biopsies of patients CONCLUSIONS: Collectively, these findings demonstrate that SAG is not a CD8+ T cell autoantigen and sharply contrast the paradigm in the pathogenesis of BCR. Therefore, the mechanism by which HLA-A29 is associated with BCR does not involve SAG |
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| Description: | Date Completed 14.02.2023 Date Revised 18.03.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2022.109219 |