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Lack of pathogenicity of immunodominant T and B cell determinants of the nicotinic acetylcholine receptor epsilon-chain.

Abstract
The nicotinic acetylcholine receptor (nAChR) is the autoantigen in seropositive myasthenia gravis (MG) that is a T cell-dependent B cell-mediated autoimmune disorder. We tested the immunogenicity and myasthenogenicity of the extracellular and first transmembrane domain of the epsilon-chain(1-221) of the nAChR in inbred and MHC congenic rat strains. Immunodominant T and B cell determinants did not induce experimental autoimmune myasthenia gravis (EAMG), although immunization resulted in strong Th1 and B cell responses, which could be mapped with overlapping peptides of the nAChR epsilon-subunit in eight different rat strains. Our data underscores the concept that immunodominant autoantigen-specific T and B cell responses can lack pathogenicity in autoimmune disease and might be of relevance for the physiological integrity of the organism.
AuthorsSusanne Gaertner, Katrien L de Graaf, Wolfgang Wienhold, Karl-Heinz Wiesmüller, Arthur Melms, Robert Weissert
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 152 Issue 1-2 Pg. 44-56 (Jul 2004) ISSN: 0165-5728 [Print] Netherlands
PMID15223236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantigens
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Peptides
  • Receptors, Nicotinic
Topics
  • Amino Acid Sequence
  • Animals
  • Animals, Congenic
  • Autoantigens (immunology)
  • B-Lymphocytes (immunology)
  • Disease Models, Animal
  • Epitopes, B-Lymphocyte (immunology)
  • Epitopes, T-Lymphocyte (immunology)
  • Humans
  • Male
  • Molecular Sequence Data
  • Myasthenia Gravis, Autoimmune, Experimental (immunology)
  • Peptides (immunology)
  • Rats
  • Rats, Inbred Lew
  • Receptors, Nicotinic (immunology)
  • Th1 Cells (immunology)

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