Nonpeptidic compounds stimulate human T cells bearing the TCR-γδ in the absence of major histocompatibility complex restriction. We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of Vγ9/Vδ 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 Vγ9/Vδ2, 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 αβ T cells, all the tested Vγ9/Vδ2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.
Functional Inactivation in the Whole Population of Human Vγ9/Vδ2 T Lymphocytes Induced By a Nonpeptidic Antagonist
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.
Martin R. Bürk, Ilaria Carena, Alena Donda, Francesca Mariani, Lucia Mori, Gennaro De Libero; Functional Inactivation in the Whole Population of Human Vγ9/Vδ2 T Lymphocytes Induced By a Nonpeptidic Antagonist. J Exp Med 6 January 1997; 185 (1): 91–98. doi: https://doi.org/10.1084/jem.185.1.91
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