T Cell Apoptosis Triggered via the CD3/T Cell Receptor Complex and Alternative Activation Pathways

1995 ◽  
pp. 1-14 ◽  
Author(s):  
D. Kabelitz ◽  
T. Pohl ◽  
K. Pechhold
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Apoptosis ◽  
Cell Receptor ◽  
Alternative Activation ◽  
Receptor Complex ◽  
T Cell Apoptosis ◽  
Activation Pathways

scholarly journals Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis.

1996 ◽  
Vol 183 (5) ◽  
pp. 2109-2117 ◽  
Author(s):  
B Combadière ◽  
M Freedman ◽  
L Chen ◽  
E W Shores ◽  
P Love ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Apoptosis ◽  
Cell Receptor ◽  
Single Chain ◽  
Tcr Signaling ◽  
T Cell Apoptosis ◽  
Zeta Chain ◽  
Src Homology ◽  
Src Homology 2 Domain

Engagement of the T cell receptor (TCR) of mature T lymphocytes can lead either to activation/proliferation responses or programmed cell death. To understand the molecular regulation of these two fundamentally different outcomes of TCR signaling, we investigated the participation of various components of the TCR-CD3 complex. We found that the TCR-zeta chain, while not absolutely required, was especially effective at promoting mature T cell apoptosis compared with the CD3 epsilon, gamma, or delta chains. We also carried out mutagenesis to address the role of the immunoreceptor tyrosine-based activation motifs (ITAMs) that are the principal signaling components found three times in the TCR-zeta chain and once in each of the CD3 epsilon, gamma, or delta chains. We found that the ability of the TCR-zeta chain to promote apoptosis results both from a quantitative effect of the presence of multiple ITAMs as well as qualitatively different contributions made by individual ITAMs. Apoptosis induced by single chain chimeras revealed that the first zeta ITAM stimulated greater apoptosis than the third zeta ITAM, and the second zeta ITAM was unable to trigger apoptosis. Because microheterogeneity in the amino acid sequence of the various ITAM motifs found in the TCR-zeta and CD3 chains predicts interactions with distinct src-homology-2-domain signaling proteins, our results suggest the possibility that individual ITAM motifs might play unique roles in TCR responses by engaging specific signaling pathways.

Glucosamine Induces Activated T Cell Apoptosis Through Reduced T Cell Receptor

2013 ◽  
Vol 78 (1) ◽  
pp. 17-27 ◽  
Author(s):  
N.-H. Chen ◽  
K. A. Cheong ◽  
C.-H. Kim ◽  
M. Noh ◽  
A.-Y. Lee
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Apoptosis ◽  
Cell Receptor ◽  
T Cell Apoptosis ◽  
Activated T Cell

scholarly journals Selective Induction of Apoptosis in Mature T Lymphocytes by Variant T Cell Receptor Ligands

1998 ◽  
Vol 187 (3) ◽  
pp. 349-355 ◽  
Author(s):  
Behazine Combadière ◽  
Caetano Reis e Sousa ◽  
Ronald N. Germain ◽  
Michael J. Lenardo
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Apoptosis ◽  
Intracellular Signaling ◽  
Fas Ligand ◽  
Complex Molecule ◽  
Major Histocompatibility Complex Molecule ◽  
Cell Receptor ◽  
T Helper 1 ◽  
T Cell Apoptosis

Activation, anergy, and apoptosis are all possible outcomes of T cell receptor (TCR) engagement. The first leads to proliferation and effector function, whereas the others can lead to partial or complete immunological tolerance. Structural variants of immunizing peptide–major histocompatibility complex molecule ligands that induce selective lymphokine secretion or anergy in mature T cells in association with altered intracellular signaling events have been described. Here we describe altered ligands for mature mouse CD4+ T helper 1 cells that lead to T cell apoptosis by the selective expression of Fas ligand (FasL) and tumor necrosis factor (TNF) without concomitant IL-2, IL-3, or interferon γ production. All ligands that stimulated cell death were found to induce FasL and TNF mRNA expression and TCR aggregation (“capping”) at the cell surface, but did not elicit a common pattern of tyrosine phosphorylation of the TCR-associated signal transduction chains. Thus, TCR ligands that uniquely trigger T cell apoptosis without inducing cytokines that are normally associated with activation can be identified.

A unique T-cell receptor complex expressed on human fetal lymphocytes displaying natural-killer-like activity

Nature ◽  
1986 ◽  
Vol 323 (6089) ◽  
pp. 638-640 ◽  
Author(s):  
P. Moingeon ◽  
A. Ythier ◽  
G. Goubin ◽  
F. Faure ◽  
A. Nowill ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex

scholarly journals Probing Lipid Interactions of the T-cell Receptor Complex: A Micropatterning Approach

2018 ◽  
Vol 114 (3) ◽  
pp. 108a
Author(s):  
Joschka Hellmeier ◽  
Florian Kellner ◽  
Gerhard Schuetz ◽  
Johannes Huppa ◽  
Eva Sevcsik
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Lipid Interactions

scholarly journals Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3ζ, the Signaling Chain of the T-Cell Receptor Complex

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 585-594 ◽  
Author(s):  
Linda A. Trimble ◽  
Judy Lieberman
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus ◽  
Specific Cytotoxicity

Although human immunodeficiency virus (HIV)-infected subjects without acquired immunodeficiency syndrome have a high frequency of HIV-specific CD8 T lymphocytes, freshly isolated lymphocytes frequently lack detectable HIV-specific cytotoxicity. However, this effector function becomes readily apparent after overnight culture. To investigate reasons for T-cell dysfunction, we analyzed T-cell expression of the cytolytic protease granzyme A and of CD3ζ, the signaling component of the T-cell receptor complex. An increased proportion of CD4 and CD8 T cells from HIV-infected donors contain granzyme A, consistent with the known increased frequency of activated T cells. In 28 HIV-infected donors with mild to advanced immunodeficiency, a substantial fraction of circulating T cells downmodulated CD3ζ (fraction of T cells expressing CD3ζ, 0.74 ± 0.16 v 1.01 ± 0.07 in healthy donors; P < .0000005). CD3ζ expression is downregulated more severely in CD8 than CD4 T cells, decreases early in infection, and correlates with declining CD4 counts and disease stage. CD3ζ expression increases over 6 to 16 hours of culture in an interleukin-2–dependent manner, coincident with restoration of viral-specific cytotoxicity. Impaired T-cell receptor signaling may help explain why HIV-specific cytotoxic T lymphocytes fail to control HIV replication.

Characterization of the CD3ζ, CD3γδ and CD3ε subunits of the T cell receptor complex in Atlantic salmon

2008 ◽  
Vol 32 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Yun Liu ◽  
Lindsey Moore ◽  
Erling Olaf Koppang ◽  
Ivar Hordvik
Keyword(s):  
T Cell ◽  
Atlantic Salmon ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex

scholarly journals Stimulation of T cells through the CD3/T-cell receptor complex: role of cytoplasmic calcium, protein kinase C translocation, and phosphorylation of pp60c-src in the activation pathway.

1987 ◽  
Vol 7 (2) ◽  
pp. 650-656 ◽  
Author(s):  
J A Ledbetter ◽  
L E Gentry ◽  
C H June ◽  
P S Rabinovitch ◽  
A F Purchio
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Solid Phase ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Receptor Complex ◽  
Kinase C ◽  
Stimulation Of

Stimulation of T cells or the Jurkat T-cell line with soluble antibodies to the CD3/T-cell receptor complex causes mobilization of cytoplasmic Ca2+, which is blocked by pertussis toxin but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and translocation of protein kinase C activity from the cytoplasm to the membrane. Such stimulation also causes phosphorylation of pp60c-src at an amino-terminal serine residue. These activities are consistent with induction of phosphatidylinositol metabolism after antibody binding. Anti-CD3 stimulation with antibody in solution, however, does not cause Jurkat cells to release interleukin 2 and blocks rather than induces proliferation of T cells. Induction of interleukin 2 production by Jurkat cells and proliferation by normal T cells requires anti-CD3 stimulation with antibody on a solid support, such as Sepharose beads or a plastic dish. Thus, we examined phosphorylation of pp60c-src after stimulation of Jurkat cells with anti-CD3 in solution or on solid phase. Both of these caused serine phosphorylation of pp60c-src that was indistinguishable even after 4 h of stimulation. These results indicate that the mode of anti-CD3 stimulation (in solution or on solid phase) controls a cellular function that modifies the consequences of signal transduction through phosphatidylinositol turnover.

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