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

Krishnamoorthy, G., Saxena, A., Mars, L. T., Domingues, H. S., Ben-Nun, A., Lassmann, H., et al. (2009). Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis. Nature Medicine, 15(6), 626-632.

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 Creators:
Krishnamoorthy, G.1, Author              
Saxena, A.2, Author
Mars, L. T.2, Author
Domingues, H. S.1, Author              
Ben-Nun, A.2, Author
Lassmann, H.2, Author
Dornmair, K.1, Author              
Mentele, R.1, Author              
Kurschus, F. C.1, Author              
Liblau, R. S.2, Author
Wekerle, H.1, Author              
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
2[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., ou_persistent22              

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 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-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.

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Language(s): eng - English
 Dates: 2009-06
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 432453
ISI: 000266731600021
 Degree: -

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Title: Nature Medicine
  Alternative Title : Nat. Med.
Source Genre: Journal
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Pages: - Volume / Issue: 15 (6) Sequence Number: - Start / End Page: 626 - 632 Identifier: ISSN: 1078-8956