scholarly journals Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jingjing Liang ◽  
Jun Lyu ◽  
Meng Zhao ◽  
Dan Li ◽  
Mingzhu Zheng ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Calcium Signalling ◽  
Cell Receptor ◽  
Proximal Region ◽  
Thymocyte Development ◽  
Crucial Component ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

Abstract Thymocyte-expressed, positive selection-associated 1 (Tespa1) is important in T cell receptor (TCR)-driven thymocyte development. Downstream of the TCR, Tespa1 is a crucial component of the linker for activation of T cells (LAT) signalosome, facilitating calcium signalling and subsequent MAPK activation. However, it is unknown how Tespa1 elicits calcium signalling. Here, we show that inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) is crucial for Tespa1-optimized, TCR-induced Ca2+ flux and thymocyte development. Upon TCR stimulation, Tespa1 directly interacts with IP3R1 and recruits it to the TCR complex, where IP3R1 is phosphorylated at Y353 by Fyn. This Tespa1-IP3R1 interaction is mediated by the F187 and F188 residues of Tespa1 and the amino-terminus of IP3R1. Tespa1-F187A/F188A mutant mice phenocopy Tespa1-deficient mice with impaired late thymocyte development due to reduced IP3R1 translocation to the TCR-proximal region. Our work elucidates the function of Tespa1 in T cell development and the regulation of TCR-induced Ca2+ signalling through IP3R1.

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.

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.

The T Cell Receptor: Its Repertoire and Role in Thymocyte Development

1987 ◽  
pp. 1-12 ◽  
Author(s):  
Philippa Marrack ◽  
Marcia McDuffie ◽  
Willi Born ◽  
Marica Blackman ◽  
Charles Hannum ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Thymocyte Development

scholarly journals In Vivo Selection of T-Cell Receptor Junctional Region Sequences by HLA-A2 Human T-Cell Lymphotropic Virus Type 1 Tax11-19 Peptide Complexes

2001 ◽  
Vol 75 (2) ◽  
pp. 1065-1071 ◽  
Author(s):  
Mineki Saito ◽  
Graham P. Taylor ◽  
Akiko Saito ◽  
Yoshitaka Furukawa ◽  
Koichiro Usuku ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Virus Type ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Human T Cell ◽  
Cdr3 Region

ABSTRACT Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8+ T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vβ CDR3 region of clonally expanded CD8+ T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.

108-OR: Islet-Derived Preproinsulin T Cell Receptor Sequences Are Present throughout the Stages of Type 1 Diabetes Development

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 108-OR
Author(s):  
ERIN E. BASCHAL ◽  
ANGELA M. MITCHELL ◽  
KRISTEN MCDANIEL ◽  
AIMON ALKANANI ◽  
TAYLOR ARMSTRONG ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Diabetes Development

scholarly journals Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1

2019 ◽  
Vol 132 (15) ◽  
pp. 1796-1801 ◽  
Author(s):  
Hui Ouyang ◽  
Fang Han ◽  
Ze-Chen Zhou ◽  
Qi-Wen Zheng ◽  
Yang-Yang Wang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Gene Polymorphisms ◽  
Cell Receptor
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