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.) |
References: | Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10719-10724. (PMID: 28893994) Nat Commun. 2016 Jun 28;7:12015. (PMID: 27352007) Lancet. 1983 Nov 12;2(8359):1115-9. (PMID: 6138647) J Exp Med. 1991 Jan 1;173(1):19-24. (PMID: 1702137) Nat Rev Genet. 2008 Jul;9(7):516-26. (PMID: 18542080) Neurology. 1997 Oct;49(4):1116-26. (PMID: 9339699) Brain. 2013 Jun;136(Pt 6):1783-98. (PMID: 23739916) Lancet. 1995 Oct 14;346(8981):1042-3. (PMID: 7475580) J Immunol. 1997 Apr 15;158(8):3746-52. (PMID: 9103439) Cell. 2018 Nov 29;175(6):1679-1687.e7. (PMID: 30343897) Clin Microbiol Rev. 2009 Apr;22(2):370-85, Table of Contents. (PMID: 19366919) Nat Med. 2000 Jan;6(1):56-61. (PMID: 10613824) Sci Immunol. 2018 Jun 8;3(24):. (PMID: 29884618) Nat Rev Neurol. 2017 Jan;13(1):25-36. (PMID: 27934854) Nat Commun. 2013;4:2039. (PMID: 23783831) Immunogenetics. 1997;46(2):104-10. (PMID: 9162096) J Neuroimmunol. 2005 Oct;167(1-2):108-19. (PMID: 16111772) Eur J Immunol. 2002 Oct;32(10):2737-47. (PMID: 12355425) Arthritis Rheum. 1987 Nov;30(11):1205-13. (PMID: 2446635) Tissue Antigens. 1991 Apr;37(4):161-4. (PMID: 1926124) J Immunol. 2001 Aug 15;167(4):2130-41. (PMID: 11489997) EMBO J. 2005 Sep 7;24(17):2968-79. (PMID: 16079912) Front Immunol. 2019 Mar 22;10:462. (PMID: 30984162) J Immunol. 2004 Mar 15;172(6):3893-904. (PMID: 15004197) Nature. 2006 Oct 5;443(7111):574-7. (PMID: 17006452) Nat Rev Immunol. 2014 Jun;14(6):377-91. (PMID: 24830344) Eur J Immunol. 2009 Aug;39(8):2088-94. (PMID: 19637200) Nat Immunol. 2009 May;10(5):514-23. (PMID: 19305396) Lancet Neurol. 2018 Feb;17(2):162-173. (PMID: 29275977) Nat Med. 1995 May;1(5):448-52. (PMID: 7585093) Bioinformatics. 2011 Apr 1;27(7):968-72. (PMID: 21300701) J Immunol. 1994 Aug 15;153(4):1665-73. (PMID: 7519208) Methods Mol Biol. 2019;1988:123-136. (PMID: 31147937) Mult Scler. 2014 Feb;20(2):165-73. (PMID: 23999606) J Virol. 2007 Jul;81(13):6777-84. (PMID: 17459939) N Engl J Med. 2008 Feb 14;358(7):676-88. (PMID: 18272891) Nature. 2002 Nov 28;420(6914):429-34. (PMID: 12459785) J Exp Med. 1993 Jul 1;178(1):27-47. (PMID: 8315383) Cell. 1995 Mar 10;80(5):695-705. (PMID: 7534214) J Exp Med. 1994 Jan 1;179(1):279-90. (PMID: 7505801) Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8. (PMID: 18503082) Eur J Immunol. 2007 Mar;37(3):602-12. (PMID: 17304631) Nucleic Acids Res. 2016 Jul 8;44(W1):W147-53. (PMID: 27190236) Nature. 2011 Aug 10;476(7359):214-9. (PMID: 21833088) Sci Transl Med. 2018 Oct 10;10(462):. (PMID: 30305453) Nature. 1992 Aug 27;358(6389):764-8. (PMID: 1380674) Front Immunol. 2017 Aug 21;8:984. (PMID: 28871256) Annu Rev Immunol. 2005;23:683-747. (PMID: 15771584) Eur J Immunol. 1996 Nov;26(11):2624-34. (PMID: 8921948) Sci Transl Med. 2015 Oct 21;7(310):310ra166. (PMID: 26491076) Immunity. 2000 Mar;12(3):233-9. (PMID: 10755610) Tissue Antigens. 1995 Oct;46(4):333-6. (PMID: 8560455) Clin Rev Allergy Immunol. 2012 Feb;42(1):102-11. (PMID: 22095454) J Clin Invest. 2018 May 1;128(5):1888-1902. (PMID: 29438107) Biochem J. 1994 Aug 1;301 ( Pt 3):847-53. (PMID: 7519851) J Immunol. 2012 Sep 15;189(6):2897-908. (PMID: 22888134) J Mol Biol. 2000 Nov 24;304(2):177-88. (PMID: 11080454) J Exp Med. 2013 Dec 16;210(13):2921-37. (PMID: 24323356) Nature. 2005 Mar 10;434(7030):238-43. (PMID: 15724150) Ann Clin Transl Neurol. 2015 Sep;2(9):875-93. (PMID: 26401510) Proc Natl Acad Sci U S A. 2016 Feb 2;113(5):1363-8. (PMID: 26787888) Cell. 2018 Sep 20;175(1):85-100.e23. (PMID: 30173916) Nature. 1991 Oct 17;353(6345):622-7. (PMID: 1656276) Annu Rev Immunol. 2015;33:787-821. (PMID: 25706097) J Autoimmun. 2019 Sep;103:102276. (PMID: 31104947) Neurol Neuroimmunol Neuroinflamm. 2019 Dec 27;7(2):. (PMID: 31882398) Proc Natl Acad Sci U S A. 1990 Oct;87(20):7968-72. (PMID: 1700423) Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450. (PMID: 30395289) Nat Rev Immunol. 2018 May;18(5):325-339. (PMID: 29292391) Immunology. 2018 Jul;154(3):394-406. (PMID: 29315598) J Immunol. 2008 Oct 15;181(8):5473-80. (PMID: 18832704) J Immunol. 2013 Nov 15;191(10):5074-84. (PMID: 24123687) J Exp Med. 1989 Mar 1;169(3):1191-6. (PMID: 2784477) Nat Immunol. 2002 Oct;3(10):940-3. (PMID: 12244309) J Exp Med. 1990 Sep 1;172(3):779-88. (PMID: 2117634) Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10713-10718. (PMID: 28893978) Nat Genet. 2015 Oct;47(10):1107-1113. (PMID: 26343388) Nature. 1992 Jul 30;358(6385):377-8. (PMID: 1641019) J Exp Med. 1998 Oct 19;188(8):1511-20. (PMID: 9782128) Science. 2019 Sep 27;365(6460):. (PMID: 31604244) J Exp Med. 2013 Nov 18;210(12):2569-82. (PMID: 24190431) Lancet. 1973 Dec 1;2(7840):1221-5. (PMID: 4128558) J Immunol Methods. 2010 Feb 28;353(1-2):93-101. (PMID: 20036243) Nat Commun. 2018 Jun 19;9(1):2397. (PMID: 29921915) N Engl J Med. 2018 Jan 11;378(2):169-180. (PMID: 29320652) J Immunol. 2006 Feb 1;176(3):1951-61. (PMID: 16424227) J Clin Invest. 1997 Jul 15;100(2):339-49. (PMID: 9218510) Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16955-16960. (PMID: 31375628) Eur J Immunol. 2012 Mar;42(3):790-8. (PMID: 22144343) Nat Methods. 2009 Nov;6(11):786-7. (PMID: 19876014) Cell. 1989 Feb 10;56(3):327-9. (PMID: 2492449) Nat Rev Neurosci. 2019 Dec;20(12):728-745. (PMID: 31712781) Nat Med. 1995 May;1(5):388. (PMID: 7585075) Trends Immunol. 2017 Nov;38(11):805-816. (PMID: 28830733) J Immunol. 2012 Oct 1;189(7):3618-30. (PMID: 22942431) J Immunol. 1998 Apr 1;160(7):3363-73. (PMID: 9531296) Cell Immunol. 2016 Jan;299:30-41. (PMID: 26653006) Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6873-8. (PMID: 10359806) |
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 |
تدمد: | 1097-4172 |
---|---|
DOI: | 10.1016/j.cell.2020.09.054 |