TY - JOUR

T1 - Superantigen and HLA-DR ligation induce phospholipase-C gamma 1 activation in class II+ T cells

AU - Kanner, S B

AU - Odum, Niels

AU - Grosmaire, L

AU - Masewicz, S

AU - Svejgaard, A

AU - Ledbetter, J A

N1 - Keywords: Antigens, Bacterial; Antigens, CD; Antigens, CD28; Antigens, Differentiation, T-Lymphocyte; Enterotoxins; Enzyme Activation; HLA-D Antigens; Humans; Lymphocyte Activation; Phosphotyrosine; Protein-Tyrosine Kinases; Staphylococcus aureus; T-Lymphocytes; Tetradecanoylphorbol Acetate; Type C Phospholipases; Tyrosine

PY - 1992

Y1 - 1992

N2 - Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA-DR) expressed on both APC and activated human T cells, and simultaneously bind to certain V beta chains of the TCR. In this report, we compared early T cell signaling events in human alloantigen-stimulated T cells when activated by HLA-DR ligation through antibody cross-linking or by direct enterotoxin superantigen binding. Both types of stimuli induced tyrosine phosphorylation of phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an increase in intracellular calcium concentration; however, superantigen-induced signaling was stronger than class II ligation alone. Antibody-mediated ligation of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased calcium mobilization, consistent with a mechanism of superantigen activity through a combination of class II and CD3/Ti signals. In addition, down-modulation of CD3 receptors with antibody demonstrated that superantigen-induced signaling events were CD3-dependent. Superantigen signaling was also class II-dependent, in that resting T cells were not responsive to direct enterotoxin stimulation. To address how early signal transducing activity correlated with T cell responsiveness, alloantigen-primed T cells were activated with immobilized class II-specific mAb or soluble superantigen. Both HLA-DR mAb-stimulated T cells and enterotoxin-treated T cells proliferated strongly in response to co-stimulation by a combination of CD28 receptor engagement and PMA addition. In addition, superantigen-induced growth was induced by CD28 receptor ligation with antibody or the B7 counter-receptor expressed on Chinese hamster ovary cells. Taken together, these results indicate that class II molecules expressed on activated T cells are directly coupled to the PLC gamma 1 signal transduction pathway, and that coligation of HLA-DR with CD3 augments T cell signaling comparable to that induced by enterotoxin superantigen. Thus, we suggest that superantigen-induced early signaling responses in activated T cells may be due in part to class II transmembrane signals induced when HLA-DR and V beta are ligated in cis.

AB - Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA-DR) expressed on both APC and activated human T cells, and simultaneously bind to certain V beta chains of the TCR. In this report, we compared early T cell signaling events in human alloantigen-stimulated T cells when activated by HLA-DR ligation through antibody cross-linking or by direct enterotoxin superantigen binding. Both types of stimuli induced tyrosine phosphorylation of phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an increase in intracellular calcium concentration; however, superantigen-induced signaling was stronger than class II ligation alone. Antibody-mediated ligation of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased calcium mobilization, consistent with a mechanism of superantigen activity through a combination of class II and CD3/Ti signals. In addition, down-modulation of CD3 receptors with antibody demonstrated that superantigen-induced signaling events were CD3-dependent. Superantigen signaling was also class II-dependent, in that resting T cells were not responsive to direct enterotoxin stimulation. To address how early signal transducing activity correlated with T cell responsiveness, alloantigen-primed T cells were activated with immobilized class II-specific mAb or soluble superantigen. Both HLA-DR mAb-stimulated T cells and enterotoxin-treated T cells proliferated strongly in response to co-stimulation by a combination of CD28 receptor engagement and PMA addition. In addition, superantigen-induced growth was induced by CD28 receptor ligation with antibody or the B7 counter-receptor expressed on Chinese hamster ovary cells. Taken together, these results indicate that class II molecules expressed on activated T cells are directly coupled to the PLC gamma 1 signal transduction pathway, and that coligation of HLA-DR with CD3 augments T cell signaling comparable to that induced by enterotoxin superantigen. Thus, we suggest that superantigen-induced early signaling responses in activated T cells may be due in part to class II transmembrane signals induced when HLA-DR and V beta are ligated in cis.

M3 - Journal article

C2 - 1385526

VL - 149

SP - 3482

EP - 3488

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -