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TCR Derived from a Polymyositis Lesion1
* Max Planck Institute of Neurobiology, Martinsried, Germany;
Institute for Clinical Neuroimmunology, Klinikum Gro
hadern, Ludwig Maximilians University, Munich, Germany;
Max Planck Institute for Immunobiology, Freiburg, Germany; and
Department of Neurology, University of Tübingen, Tübingen, Germany
To investigate the role of 
T cells in human autoimmune
disease we expressed and characterized a TCR from an autoimmune
tissue lesion. The TCR was first identified in a rare form of
polymyositis characterized by a monoclonal infiltrate of T cells
which invaded and destroyed skeletal muscle fibers. The
V1.3-J1-C1/V2-J3 TCR cDNA of the original muscle
invasive T cell clone was reconstructed from unrelated cDNA and
transfected into the mouse hybridoma
BW58
--. Appropriate anti-human
TCR Abs stimulated the TCR transfectants to produce IL-2, thus
demonstrating that the human TCR functionally interacted with
murine signaling components. The transfected V1.3/V2 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 TCR transfectants
with defined exchanges in different positions of both TCR chains, we
showed that the 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 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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