Functional inactivation in the whole population of human V gamma 9/V delta 2 T lymphocytes induced by a nonpeptidic antagonist.
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 beta 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.
Bürk
M R
MR
Department of Research, University Hospital, Basel, Switzerland.
Carena
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Donda
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Mariani
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Mori
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De Libero
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D019794:2,3-Diphosphoglycerate; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004163:Diphosphoglyceric Acids / Q000494:pharmacology*; D005434:Flow Cytometry; D045782:Hemiterpenes; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004163:Diphosphoglyceric Acids; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D019794:2,3-Diphosphoglycerate; C004809:isopentenyl pyrophosphate