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© The Rockefeller University Press, 0022-1007/1997/1/91/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 1, January 6, 1997 91-98


Articles

Functional Inactivation in the Whole Population of Human V{gamma}9/V{delta}2 T Lymphocytes Induced By a Nonpeptidic Antagonist

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 V{gamma}9/V{delta} 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 V{gamma}9/V{delta}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}β T cells, all the tested V{gamma}9/V{delta}2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.


Address correspondence to Gennaro De Libero, Experimental Immunology, Department of Research, University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.

This work was supported by the Swiss National Fund grants No. 31-36450-92 and No. 31-045518.95 to G. De Libero and the Marie-Heim Vögtlin grant No. 32-38848-93 to L. Mori.

1Abbreviations used in this paper: DPG, 2,3-diphosphoglyceric acid; E/T, effector/target; IPP, isopentenylpyrophosphate; MFI, median fluorescence intensity; M. tub., Mycobacterium tuberculosis.


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