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Zusammenfassung:
To investigate the role of γδ T cells in human autoimmune disease we expressed and characterized a γδ 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 Vγ1.3-Jγ1-Cγ1/Vδ2-Jδ3 TCR cDNA of the original muscle invasive γδ T cell clone was reconstructed from unrelated cDNA and transfected into the mouse hybridoma BW58α₋β₋. Appropriate anti-human γδ TCR Abs stimulated the TCR transfectants to produce IL-2, thus demonstrating that the human γδ TCR functionally interacted with murine signaling components. The transfected Vγ1.3/Vδ2 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 γδ TCR transfectants with defined exchanges in different positions of both TCR chains, we showed that the γδ 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 γδ TCR directly derived from an autoimmune tissue lesion. The strategy used in this study may be applicable to other autoimmune diseases.
