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Nature MedicineVolume 15, Issue 6, 8 June 2009, Pages 626-632

Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis(Article)

  • Krishnamoorthy, G.,
  • Saxena, A.,
  • Mars, L.T.,
  • Domingues, H.S.,
  • Mentele, R.,
  • Ben-Nun, A.,
  • Lassmann, H.,
  • Dornmair, K.,
  • Kurschus, F.C.,
  • Liblau, R.S.,
  • Wekerle, H.
  • View Correspondence (jump link)
  • aDepartment of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany
  • bInstitut National de la Santé et de la Recherche Médicale, Unité 563, Université Toulouse III, Paul-Sabatier, Toulouse, France
  • cPhD Program in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
  • dInstitute of Clinical Neuroimmunology, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany
  • eDepartment for Protein Analytics, Max Planck Institute of Biochemistry, Martinsried, Germany
  • fDepartment of Immunology, Weizmann Institute of Science, Rehovot, Israel
  • gCenter for Brain Research, Medical University of Vienna, Vienna, Austria
  • hI. Medizinische Klinik und Poliklinik, Johannes Gutenberg Universität, Mainz, Germany

Abstract

We describe here the paradoxical development of spontaneous experimental autoimmune encephalomyelitis (EAE) in transgenic mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell antigen receptor (TCR) in the absence of MOG. We report that in Mog-deficient mice (Mog /), the autoimmune response by transgenic T cells is redirected to a neuronal cytoskeletal self antigen, neurofilament-M (NF-M). Although components of radically different protein classes, the cross-reacting major histocompatibility complex I-A b -restricted epitope sequences of MOG 35-55 and NF-M 18-30 share essential TCR contact positions. This pattern of cross-reaction is not specific to the transgenic TCR but is also commonly seen in MOG 35-55 -I-A b -reactive T cells. We propose that in the C57BL/6 mouse, MOG and NF-M response components add up to overcome the general resistance of this strain to experimental induction of autoimmunity. Similar cumulative responses against more than one autoantigen may have a role in spontaneously developing human autoimmune diseases. © 2009 Nature America, Inc. All rights reserved.

Indexed keywords

EMTREE drug terms:myelin oligodendrocyte glycoproteinneurofilament M proteinT lymphocyte receptor
EMTREE medical terms:allergic encephalomyelitisanimal cellanimal experimentanimal modelarticleautoimmunitycontrolled studycross reactionin vivo studymajor histocompatibility complexmousemultiple sclerosisnonhumanpriority journalprotein deficiencyprotein expressionT lymphocytewild type
MeSH:Amino Acid SequenceAnimalsAutoantigensCross ReactionsDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalMiceMice, Inbred C57BLMice, TransgenicMolecular Sequence DataMultiple SclerosisMyelin SheathMyelin-Associated GlycoproteinNeurofilament ProteinsReceptors, Antigen, T-CellT-Lymphocytes
Species Index:MusMus musculus

Chemicals and CAS Registry Numbers:

Autoantigens; Myelin-Associated Glycoprotein; Neurofilament Proteins; Receptors, Antigen, T-Cell; neurofilament protein M, 111365-29-8; oligodendrocyte-myelin glycoprotein

Funding details

Funding sponsor Funding number Acronym
Fundação para a Ciência e a Tecnologia
See opportunities
National Multiple Sclerosis Society
See opportunities		RG3195B8/2
Fuel Cell Technologies ProgramSFRH/BD/15885/2005FCT
Israel Science FoundationISF
Deutsche Forschungsgemeinschaft
See opportunities		SFB,A1,B6
PL 018637

  • 1

    MogCre/Cre, Nefm–/–, 2D2 and Mog–/– mice were generously provided by A. Waisman (Johannes Gutenberg University of Mainz), J.-P. Julien (Laval University), V.K. Kuchroo (Harvard Medical School) and D. Pham-Dinh (INSERM UMR 546). We thank F. Lottspeich for granting us permission to use his mass spectrometer. We thank L. Penner and I. Arnold-Ammer for technical support. This project was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereiche (SFB) 571, Projects A1 and B6) and the Max Planck Society. H.S.D. is supported by a PhD fellowship (Portuguese Fundac¸ão para a Ciência ea Tecnologia (FCT) program SFRH/BD/15885/2005). Part of the study (conducted by H.W., R.L. and H.L.) was funded by the EU Project Neuropromise (PL 018637), and A.B.-N. was supported by the Israel Science Foundation and the National Multiple Sclerosis Society of New York (RG3195B8/2). A.B.-N. is an Alexander von Humboldt Prize Awardee.

  • ISSN: 10788956
  • CODEN: NAMEF
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1038/nm.1975
  • PubMed ID: 19483694
  • Document Type: Article

  Wekerle, H.; Department of Neuroimmunology, Max Planck Institute of Neurobiology, Germany;
© Copyright 2009 Elsevier B.V., All rights reserved. © MEDLINE® is the source for the MeSH terms of this document.

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