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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents

ID: 432453.0, MPI für Neurobiologie / Neuroimmunology
Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
Authors: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.
Date of Publication (YYYY-MM-DD):2009-06
Title of Journal:Nature Medicine
Journal Abbrev.:Nat. Med.
Issue / Number:6
Start Page:626
End Page:632
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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-M18-30 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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)
MPI für Biochemie/Independent Research Groups/Protein Analytics (F. Lottspeich)
External Affiliations:[Saxena, Amit; Mars, Lennart T.; Liblau, Roland S.] Univ Toulouse 3, INSERM, U563, F-31062 Toulouse, France.; [Domingues, Helena S.] Univ Coimbra, Ctr Neurosci & Cell Biol, Program Expt Biol & Biomed, Coimbra, Portugal.; [Mentele, Reinhard; Dornmair, Klaus] Univ Munich, Univ Hosp Grosshadern, Inst Clin Neuroimmunol, Munich, Germany.; Ben-Nun, Avraham] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.; [Lassmann, Hans] Med Univ Vienna, Ctr Brain Res, Vienna, Austria.
Identifiers:ISI:000266731600021 [ID No:1]
ISSN:1078-8956 [ID No:2]
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