Differential activation of human gammadelta cells by nonpeptide phosphoantigens.

Abstract:

:Human T cells expressing Vgamma9Ndelta2-encoded TCR recognize several nonpeptide phosphoantigens in the absence of major histocompatibility complex restriction. As these cells respond differentially to increasing concentrations of structurally related phosphoantigens, such ligands constitute agonists of different strengths. By analyzing early cellular events and late effector responses of gammadelta T cells, we compared their patterns of stimulation by weak, medium and strong phosphoantigen agonists. We found that, although the early metabolic activation as assessed by cytosensor microphysiometry directly reflects the intensity of subsequent effector response by gammadelta cells, TCR down-modulation is dissociated from the latter. Weak and mid-range phosphoantigen agonists induce a time- and dose-dependent down-modulation of the gammadelta TCR, whereas strong phosphoantigen agonists induce little or no TCR down-regulation. This indicates that gammadelta TCR down-modulation does not match the extent of TCR signaling as assessed by microphysiometry or conventional effector responses (TNF-alpha production and cytotoxicity). This differential pattern of gammadelta cell activation by phosphoantigens could explain the stronger potencies of some of these agonists.

journal_name

Eur J Immunol

authors

Sireci G,Espinosa E,Di Sano C,Dieli F,Fournié JJ,Salerno A

doi

10.1002/1521-4141(200105)31:5<1628::AID-IMMU1628>3

keywords:

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

1628-35

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

31

pub_type

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