T Cell Receptor Signalling Inspired Kernel Density Estimation and Anomaly Detection

2009 ◽  
pp. 122-135 ◽  
Author(s):  
Nick D. L. Owens ◽  
Andy Greensted ◽  
Jon Timmis ◽  
Andy Tyrrell
Keyword(s):  
T Cell ◽  
Anomaly Detection ◽  
Density Estimation ◽  
T Cell Receptor ◽  
Kernel Density Estimation ◽  
Kernel Density ◽  
Cell Receptor ◽  
Receptor Signalling

scholarly journals Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1

2021 ◽  
Vol 22 (11) ◽  
pp. 5816
Author(s):  
Suresh Velnati ◽  
Sara Centonze ◽  
Federico Girivetto ◽  
Gianluca Baldanzi
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Adaptor Protein ◽  
Diacylglycerol Kinase ◽  
Cell Receptor ◽  
Lymphoproliferative Disease ◽  
Disease Type ◽  
T Cell Response ◽  
Receptor Signalling

Diacylglycerol kinases are intracellular enzymes that control the balance between the secondary messengers diacylglycerol and phosphatidic acid. DGKα and DGKζ are the prominent isoforms that restrain the intensity of T cell receptor signalling by metabolizing PLCγ generated diacylglycerol. Thus, their activity must be tightly controlled to grant cellular homeostasis and refine immune responses. DGKα is specifically inhibited by strong T cell activating signals to allow for full diacylglycerol signalling which mediates T cell response. In X-linked lymphoproliferative disease 1, deficiency of the adaptor protein SAP results in altered T cell receptor signalling, due in part to persistent DGKα activity. This activity constrains diacylglycerol levels, attenuating downstream pathways such as PKCθ and Ras/MAPK and decreasing T cell restimulation induced cell death. This is a form of apoptosis triggered by prolonged T cell activation that is indeed defective in CD8+ cells of X-linked lymphoproliferative disease type 1 patients. Accordingly, inhibition or downregulation of DGKα activity restores in vitro a correct diacylglycerol dependent signal transduction, cytokines production and restimulation induced apoptosis. In animal disease models, DGKα inhibitors limit CD8+ expansion and immune-mediated tissue damage, suggesting the possibility of using inhibitors of diacylglycerol kinase as a new therapeutic approach.

scholarly journals Anomaly Detection Using Local Kernel Density Estimation and Context-Based Regression

2020 ◽  
Vol 32 (2) ◽  
pp. 218-233 ◽  
Author(s):  
Weiming Hu ◽  
Jun Gao ◽  
Bing Li ◽  
Ou Wu ◽  
Junping Du ◽  
...  
Keyword(s):  
Anomaly Detection ◽  
Density Estimation ◽  
Kernel Density Estimation ◽  
Kernel Density

Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+CDS+thymocytes

Nature ◽  
1995 ◽  
Vol 374 (6521) ◽  
pp. 474-476 ◽  
Author(s):  
Klaus-Dieter Fischer ◽  
Antanina Zmuidzinas ◽  
Sandra Gardner ◽  
Mariano Barbacid ◽  
Alan Bernstein ◽  
...  
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signalling ◽  
Selection Of

scholarly journals Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling

Brain ◽  
2010 ◽  
Vol 133 (2) ◽  
pp. 375-388 ◽  
Author(s):  
Wei Hu ◽  
Stefan Nessler ◽  
Bernhard Hemmer ◽  
Todd N. Eagar ◽  
Lawrence P. Kane ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Autoimmune Disease ◽  
Prion Protein ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signalling

Antiproliferative action of interferon-α requires components of T-cell-receptor signalling

Nature ◽  
10.1038/37648 ◽  
1997 ◽  
Vol 390 (6660) ◽  
pp. 629-632 ◽  
Author(s):  
Emanuel F. Petricoin ◽  
Satoshi Ito ◽  
Brandi L. Williams ◽  
Susette Audet ◽  
Louis F. Stancato ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Interferon Α ◽  
Receptor Signalling ◽  
Antiproliferative Action

scholarly journals T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling?

1998 ◽  
Vol 333 (3) ◽  
pp. 615-619 ◽  
Author(s):  
Junji HIROTA ◽  
Masashi BABA ◽  
Mineo MATSUMOTO ◽  
Teiichi FURUICHI ◽  
Kiyoshi TAKATSU ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cell Phenotype ◽  
Receptor Signalling ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

Stimulation of T-cells via the T-cell receptor (TCR) complex is accompanied by an increase in intracellular Ca2+ concentration ([Ca2+]i). Recently, it was reported that a stable transformant of the human T-cell line, Jurkat, expressing an antisense cDNA construct of inositol 1,4,5-trisphosphate receptor (IP3R) type 1 (IP3R1), failed to demonstrate increased [Ca2+]i or interleukin-2 production after TCR stimulation and was also resistant to apoptotic stimuli. This cell line lacked IP3R1 expression, but expressed the type-2 and -3 receptors, IP3R2 and IP3R3 respectively [Jayaraman, Ondriasova, Ondrias, Harnick and Marks (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 6007–6011, and Jayaraman and Marks (1997) Mol. Cell. Biol. 17, 3005–3012]. The authors concluded that IP3R1 is essential for TCR signalling and suggested that Ca2+ release via IP3R1 is a critical mediator of apoptosis. To establish whether a loss of IP3R1 function in T-cells occurred in vivo and in vitro, we investigated Ca2+ signalling after TCR stimulation and the properties of T-cells using IP3R1-deficient (IP3R1-/-) mice. As IP3R1-/- mice die at weaning, we transplanted bone marrow cells of IP3R1-/- mice into irradiated wild-type mice. Western blot analysis showed that the recipient IP3R1-containing (IP3R1+/+) lymphocytes were replaced by the donor IP3R1-/- lymphocytes after transplantation and that expression of IP3R2 and IP3R3 was unaltered. In contrast with the previous reports, T-cells lacking IP3R1 were able to mobilize Ca2+ from intracellular Ca2+ stores after stimulation via the TCR. We observed no significant differences between IP3R1+/+ and IP3R1-/- T-cells in terms of the number of thymocytes and splenocytes, the proportion of the T-cell phenotype, proliferative response to anti-CD3 monoclonal antibody (mAb) stimulation and cell viability. Therefore IP3R1 is not essential for T-cell development and function.

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