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T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis

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Abstract

Chronic relapsing paralysis and demyelination within the central nervous system (CNS), features associated with the human disease multiple sclerosis (MS)1–4, develop in mice after injection of murine T-cell clones specific for the autoantigen myelin basic protein (MBP)5,6. We examined the fine specificity of three independently derived encephalitogenic T-cell clones using synthetic polypeptides derived from portions of the N-terminal sequence of MBP. These clones appear functionally identical; they all respond to an epitope in the N-terminal nine amino acid residues in association with the same class II (I-A) molecules of the major histocompatibility complex (MHC). Both the N-terminal acetyl moiety and the first residue (Ala) are necessary for recognition. Only N-terminal MBP peptides recognized by these clones were found to cause encephalomyelitis (EAE) in vivo. These results show that the N-terminal MBP-specific T lymphocytes that mediate autoimmune encephalomyelitis are a small population with a limited repertoire; they all recognise the same combination of MHC and target.

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Authors and Affiliations

  1. Departments of Neurology and Pediatrics, Stanford University, Stanford, California, 94305, USA

    Scott S. Zamvil, Dennis J. Mitchell, Anne C. Moore, Kumiko Kitamura & Lawrence Steinman

  2. The Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London, WC2A 3PX, UK

    Jonathan B. Rothbard

Authors
  1. Scott S. Zamvil
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  2. Dennis J. Mitchell
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  3. Anne C. Moore
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  4. Kumiko Kitamura
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  5. Lawrence Steinman
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  6. Jonathan B. Rothbard
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Zamvil, S., Mitchell, D., Moore, A. et al. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324, 258–260 (1986). https://doi.org/10.1038/324258a0

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  • DOI: https://doi.org/10.1038/324258a0

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