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Functional inactivation in the whole population of human V gamma 9/V delta 2 T lymphocytes induced by a nonpeptidic antagonist.

Bürk MR, Carena I, Donda A, Mariani F, Mori L, De Libero G - J. Exp. Med. (1997)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Research, University Hospital, Basel, Switzerland.

ABSTRACT
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.

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Upon DPG treatment, tyrosine phosphorylation  of TCR-associated proteins is  reduced when compared to IPP  stimulation. Vγ9/Vδ2 T cells  were incubated for 10 min with  either medium (C), 100 μM  IPP, 1 mM DPG, or 1 μg/ml  PHA. Protein tyrosine phosphorylation is visualized by immunoblotting of total cell lysates. Similar results were obtained in four  independent experiments using  Vγ9/Vδ2 cell lines and clones.  IPP and DPG did not induce any  protein tyrosine phosphorylation in TCR αβ cells (data not  shown).
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Figure 6: Upon DPG treatment, tyrosine phosphorylation of TCR-associated proteins is reduced when compared to IPP stimulation. Vγ9/Vδ2 T cells were incubated for 10 min with either medium (C), 100 μM IPP, 1 mM DPG, or 1 μg/ml PHA. Protein tyrosine phosphorylation is visualized by immunoblotting of total cell lysates. Similar results were obtained in four independent experiments using Vγ9/Vδ2 cell lines and clones. IPP and DPG did not induce any protein tyrosine phosphorylation in TCR αβ cells (data not shown).

Mentions: Alterations of the TCR proximal signals have been previously described for modified peptide ligands which induce unresponsiveness in TCR αβ clones (17, 18). To investigate whether early signals are also altered in γδ T cells, the IPP- and DPG-induced protein tyrosine phosphorylation patterns were compared. A similar spectrum of phosphorylated proteins was detected (Fig. 6). However, the overall level of phosphorylation induced by DPG was quantitatively less than that induced by IPP.


Functional inactivation in the whole population of human V gamma 9/V delta 2 T lymphocytes induced by a nonpeptidic antagonist.

Bürk MR, Carena I, Donda A, Mariani F, Mori L, De Libero G - J. Exp. Med. (1997)

Upon DPG treatment, tyrosine phosphorylation  of TCR-associated proteins is  reduced when compared to IPP  stimulation. Vγ9/Vδ2 T cells  were incubated for 10 min with  either medium (C), 100 μM  IPP, 1 mM DPG, or 1 μg/ml  PHA. Protein tyrosine phosphorylation is visualized by immunoblotting of total cell lysates. Similar results were obtained in four  independent experiments using  Vγ9/Vδ2 cell lines and clones.  IPP and DPG did not induce any  protein tyrosine phosphorylation in TCR αβ cells (data not  shown).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196105&req=5

Figure 6: Upon DPG treatment, tyrosine phosphorylation of TCR-associated proteins is reduced when compared to IPP stimulation. Vγ9/Vδ2 T cells were incubated for 10 min with either medium (C), 100 μM IPP, 1 mM DPG, or 1 μg/ml PHA. Protein tyrosine phosphorylation is visualized by immunoblotting of total cell lysates. Similar results were obtained in four independent experiments using Vγ9/Vδ2 cell lines and clones. IPP and DPG did not induce any protein tyrosine phosphorylation in TCR αβ cells (data not shown).
Mentions: Alterations of the TCR proximal signals have been previously described for modified peptide ligands which induce unresponsiveness in TCR αβ clones (17, 18). To investigate whether early signals are also altered in γδ T cells, the IPP- and DPG-induced protein tyrosine phosphorylation patterns were compared. A similar spectrum of phosphorylated proteins was detected (Fig. 6). However, the overall level of phosphorylation induced by DPG was quantitatively less than that induced by IPP.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Research, University Hospital, Basel, Switzerland.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus