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  An autoreactive gamma delta TCR derived from a polymyositis lesion

Wiendl, H., Malotka, J., Holzwarth, B., Weltzien, H. U., Wekerle, H., Hohlfeld, R., et al. (2002). An autoreactive gamma delta TCR derived from a polymyositis lesion. Journal of Immunology, 169(1), 515-521.

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 Creators:
Wiendl, Heinz1, Author           
Malotka, Joachim1, Author           
Holzwarth, B.2, Author
Weltzien, H. U.2, Author
Wekerle, Hartmut1, Author           
Hohlfeld, Reinhard1, Author           
Dornmair, Klaus1, Author           
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
2Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152; Martinsried, Germany; Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany; Univ Tuebingen, Dept Neurol, D-7400 Tuebingen, Germany; Max Planck Inst Immunbiol, D-7800 Freiburg, Germany; Univ Munich, Klinikum Grosshadern, Inst Clin Neurimmunol, D-8000 Munich, Germany, ou_persistent22              

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 Abstract: To investigate the role of gammadelta T cells in human autoimmune disease we expressed and characterized a gammadelta TCR from an autoimmune tissue lesion. The TCR was first identified in a rare form of polymyositis characterized by a monoclonal infiltrate of gammadelta T cells which invaded and destroyed skeletal muscle fibers. The Vgamma1.3-Jgamma1- Cgamma1/Vdelta2-Jdelta3 TCR cDNA of the original muscle invasive gammadelta T cell clone was reconstructed from unrelated cDNA and transfected into the mouse hybridoma BW58alpha(-)beta(-). Appropriate anti-human gammadelta TCR Abs stimulated the TCR transfectants to produce IL-2, thus demonstrating that the human gammadelta TCR functionally interacted with murine signaling components. The transfected Vgamma1.3/Vdelta2 TCR recognized a cytosolic protein expressed in cultured human myoblasts and TE671 rhabdomyosarcoma cells. The Ag was recognized in the absence of presenting cells. Using a panel of control gammadelta TCR transfectants with defined exchanges in different positions of both TCR chains, we showed that the gammadelta TCR recognized its Ag in a TCR complementarity-determining region 3-dependent way. To our knowledge, this is the first example of a molecularly defined gammadelta TCR directly derived from an autoimmune tissue lesion. The strategy used in this study may be applicable to other autoimmune diseases.

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Language(s): eng - English
 Dates: 2002-07-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 10129
ISI: 000176360400064
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Title: Journal of Immunology
  Alternative Title : J. Immunol.
Source Genre: Journal
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Pages: - Volume / Issue: 169 (1) Sequence Number: - Start / End Page: 515 - 521 Identifier: ISSN: 0022-1767