The Journal of Experimental Medicine
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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/91/08 $2.00
Volume 185 January 1997 91-98

Functional Inactivation in the Whole Population of Human Vgamma 9/Vdelta 2 T Lymphocytes Induced By a Nonpeptidic Antagonist

By Martin R. Bürk, Ilaria Carena, Alena Donda, Francesca Mariani, Lucia Mori, and Gennaro De Libero

From Experimental Immunology, Department of Research, University Hospital, 4031 Basel, Switzerland

Nonpeptidic compounds stimulate human T cells bearing the TCR-gamma delta in the absence of major histocompatibility complex restriction. We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of Vgamma 9/Vdelta T cells ex vivo, antagonizes the same cell population after repetitive activation. Stimulation with DPG results in partial early protein tyrosine phosphorylation and a prolonged, but reversible, state of unresponsiveness to agonist ligands in Vgamma 9/Vdelta 2, but not in other T cells. These findings show that TCR antagonism is a general phenomenon of T cells. However, in contrast to the clonal specificity of altered peptides antagonizing alpha beta T cells, all the tested Vgamma 9/Vdelta 2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.


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