More MS news articles for June 2002

An Autoreactive gammadelta TCR Derived from a Polymyositis Lesion

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12077283&dopt=Abstract

J Immunol 2002 Jul 1;169(1):515-521
Wiendl H, Malotka J, Holzwarth B, Weltzien HU, Wekerle H, Hohlfeld R, Dornmair K.
Max Planck Institute of Neurobiology, Martinsried, Germany. Institute for Clinical Neuroimmunology, Klinikum Grobetahadern, Ludwig Maximilians University, Munich, Germany. Max Planck Institute for Immunobiology, Freiburg, Germany. Department of Neurology, University of Tubingen, Tubingen, Germany.

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.