6533b828fe1ef96bd12877a0

RESEARCH PRODUCT

Differential activation of human γ δ cells by nonpeptide phosphoantigens

subject

description

Human T cells expressing Vγ9/Vδ2-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 γ δ 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 cytosensormicrophysiometry directly reflects the intensity of subsequent effector response by γ δ cells, TCR down-modulation is dissociated from the latter. Weak and mid-range phosphoantigen agonistsinduce a time- and dose-dependent down-modulation of the γ δ TCR, whereas strong phosphoantigen agonists induce little or no TCR down-regulation. This indicates that γ δ TCR down-modulation does not match the extent of TCR signaling as assessed by microphysiometry or conventional effector responses (TNF-α production and cytotoxicity). This differential pattern of γ δ cell activation by phosphoantigens could explain the stronger potencies of some of these agonists.