An autoreactive gamma delta TCR derived from a polymyositis lesion.
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.
Wiendl
Heinz
H
Max Planck Institute of Neurobiology, Martinsried, Germany.
Malotka
Joachim
J
Holzwarth
Brigitte
B
Weltzien
Hans-Ulrich
HU
Wekerle
Hartmut
H
Hohlfeld
Reinhard
R
Dornmair
Klaus
K
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics / Q000502:physiology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D017285:Polymyositis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D001324:Autoantigens; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D009124:Muscle Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta