دورية أكاديمية
HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis.
| العنوان: | HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. |
|---|---|
| المؤلفون: | Wang J; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Jelcic I; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Mühlenbruch L; Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen 72076, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen 72076, Germany; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tübingen, Tübingen 72076, Germany., Haunerdinger V; Pediatric Stem Cell Transplantation, University Children's Hospital Zurich, Zurich 8032, Switzerland., Toussaint NC; NEXUS Personalized Health Technologies, ETH Zurich, Zurich 8093, Switzerland; Swiss Institute of Bioinformatics, Zurich, Switzerland., Zhao Y; Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, MD 20850, USA., Cruciani C; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Faigle W; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Naghavian R; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Foege M; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Binder TMC; HLA Laboratory of the Stefan Morsch Foundation (SMS), Birkenfeld 55765, Germany., Eiermann T; Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Opitz L; Functional Genomics Center Zurich, Swiss Federal Institute of Technology and University of Zurich, Zurich 8057, Switzerland., Fuentes-Font L; Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK., Reynolds R; Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK., Kwok WW; Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA., Nguyen JT; One Lambda, Inc., a part of Transplant Diagnostics Thermo Fisher Scientific, 22801 Roscoe Blvd., West Hills, CA 91304, USA., Lee JH; One Lambda, Inc., a part of Transplant Diagnostics Thermo Fisher Scientific, 22801 Roscoe Blvd., West Hills, CA 91304, USA., Lutterotti A; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Münz C; Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich 8057, Switzerland., Rammensee HG; Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen 72076, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen 72076, Germany; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tübingen, Tübingen 72076, Germany., Hauri-Hohl M; Pediatric Stem Cell Transplantation, University Children's Hospital Zurich, Zurich 8032, Switzerland., Sospedra M; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland., Stevanovic S; Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen 72076, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen 72076, Germany; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tübingen, Tübingen 72076, Germany., Martin R; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland. Electronic address: roland.martin@usz.ch. |
| المصدر: | Cell [Cell] 2020 Nov 25; Vol. 183 (5), pp. 1264-1281.e20. Date of Electronic Publication: 2020 Oct 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| مواضيع طبية MeSH: | HLA-DR Serological Subtypes/*immunology , Multiple Sclerosis/*immunology , T-Lymphocytes/*immunology, Adult ; Aged ; Alleles ; Antigens/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cross Reactions/immunology ; Female ; Humans ; Immunologic Memory ; Male ; Middle Aged ; Monocytes/immunology ; Peptides/immunology ; Proteome/metabolism ; Young Adult |
| مستخلص: | The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4 + T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4 + T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4 + T cells in MS. Competing Interests: Declaration of Interests R.M. received unrestricted grants (Biogen and Novartis) and compensation for advice/lecturing (Biogen, Novartis, Sanofi Genzyme, Merck, Hoffmann La Roche, Neuway, CellProtect, and Third Rock Ventures). R.M., M.S., and A.L. are listed as inventor on several NIH- and University of Zurich-held patents and are co-founders and co-owners of Cellerys. I.J. received compensation for advice by Sanofi Genzyme, none of which has affected this work. R.M. and M.S. are listed as co-inventors on a patent on “Immunodominant proteins and fragments in autoimmune diseases,” including RAGSRP2. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.) |
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| فهرسة مساهمة: | Keywords: B cells; HLA cross-restriction; HLA-DR-derived self-peptides; HLA-DR15 molecules; T cell repertoire; T cells; autoimmune disease; autoreactive CD4+; cross-reactivity; immunopeptidome; multiple sclerosis |
| المشرفين على المادة: | 0 (Antigens) 0 (HLA-DR Serological Subtypes) 0 (HLA-DR15 antigen) 0 (Peptides) 0 (Proteome) |
| تواريخ الأحداث: | Date Created: 20201022 Date Completed: 20210519 Latest Revision: 20210519 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7707104 |
| DOI: | 10.1016/j.cell.2020.09.054 |
| PMID: | 33091337 |
| قاعدة البيانات: | MEDLINE |
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