دورية أكاديمية
أعرض في EDS

Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis.

التفاصيل البيبلوغرافية
العنوان: Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis.
المؤلفون: Venema WJ; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands., Hiddingh S; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands., Janssen GMC; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands., Ossewaarde-van Norel J; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands., van Loon ND; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands., de Boer JH; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands., van Veelen PA; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands., Kuiper JJW; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands. Electronic address: J.J.W.Kuiper@umcutrecht.nl.
المصدر: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2023 Feb; Vol. 247, pp. 109219. Date of Electronic Publication: 2022 Dec 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 100883537 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-7035 (Electronic) Linking ISSN: 15216616 NLM ISO Abbreviation: Clin Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Orlando, FL : Academic Press, c1999-
مواضيع طبية MeSH: Chorioretinitis*, Humans ; Birdshot Chorioretinopathy ; Arrestin ; HLA-A Antigens ; Retina ; CD8-Positive T-Lymphocytes ; Peptides/metabolism ; Autoantigens ; Aminopeptidases ; Minor Histocompatibility Antigens
مستخلص: 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.
(Copyright © 2022. Published by Elsevier Inc.)
المشرفين على المادة: 0 (HLA-A29 antigen)
0 (Arrestin)
0 (HLA-A Antigens)
0 (Peptides)
0 (Autoantigens)
EC 3.4.11.- (ERAP1 protein, human)
EC 3.4.11.- (Aminopeptidases)
0 (Minor Histocompatibility Antigens)
EC 3.4.11.- (ERAP2 protein, human)
تواريخ الأحداث: Date Created: 20221229 Date Completed: 20230214 Latest Revision: 20230318
رمز التحديث: 20231215
DOI: 10.1016/j.clim.2022.109219
PMID: 36581221
قاعدة البيانات: MEDLINE
الوصف
تدمد:1521-7035
DOI:10.1016/j.clim.2022.109219