The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins in T-cell activation

2002 ◽  
Vol 9 (2-4) ◽  
pp. 93-96 ◽  
Author(s):  
Rolf Loertscher ◽  
Paula Lavery
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Activation ◽  
Phosphatidyl Inositol ◽  
Surface Proteins ◽  
Cell Surface Proteins

scholarly journals Generation and Characterization of Ecto-ADP-Ribosyltransferase ART2.1/ART2.2-Deficient Mice

2002 ◽  
Vol 22 (21) ◽  
pp. 7535-7542 ◽  
Author(s):  
Wiebke Ohlrogge ◽  
Friedrich Haag ◽  
Jürgen Löhler ◽  
Michel Seman ◽  
Dan R. Littman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tissue Injury ◽  
Surface Proteins ◽  
Cell Functions ◽  
Arginine Residues ◽  
Deficient Mice

ABSTRACT This is the first study reporting the inactivation of a member of the mouse gene family of toxin-related ecto-ADP-ribosyltransferases (ARTs). Transfer of the ADP-ribose moiety from NAD onto extracellular arginine residues on T-cell membrane proteins is mediated by glycosylphosphatidylinositol-linked cell surface ARTs. Exposure of T cells to ecto-NAD blocks T-cell activation and induces T-cell apoptosis. To determine a possible role of ecto-ART2.1 and ART2.2 in these processes, we generated ART2.1/ART2.2 double-knockout mice. ART2-deficient mice were healthy and fertile and showed normal development of lymphoid organs. ART2-deficient T cells showed a dramatically reduced capacity to ADP-ribosylate cell surface proteins, indicating that most if not all ART activity on the T-cell surface can be attributed to the ART2s. Moreover, ART2-deficient T cells were completely resistant to NAD-induced apoptosis and partially resistant to NAD-mediated suppression of proliferation. These results demonstrate that the ART2 ectoenzymes are an essential component in the regulation of T-cell functions by extracellular NAD, e.g., following release of NAD upon lysis of cells in tissue injury and inflammation.

scholarly journals Microclusters as T Cell Signaling Hubs: Structure, Kinetics, and Regulation

2021 ◽  
Vol 8 ◽  
Author(s):  
Lakshmi Balagopalan ◽  
Kumarkrishna Raychaudhuri ◽  
Lawrence E. Samelson
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vesicular Trafficking ◽  
Image Resolution ◽  
Live Cells ◽  
Cell Surface Signaling ◽  
Kinetics Of

When T cell receptors (TCRs) engage with stimulatory ligands, one of the first microscopically visible events is the formation of microclusters at the site of T cell activation. Since the discovery of these structures almost 20 years ago, they have been studied extensively in live cells using confocal and total internal reflection fluorescence (TIRF) microscopy. However, due to limits in image resolution and acquisition speed, the spatial relationships of signaling components within microclusters, the kinetics of their assembly and disassembly, and the role of vesicular trafficking in microcluster formation and maintenance were not finely characterized. In this review, we will summarize how new microscopy techniques have revealed novel insights into the assembly of these structures. The sub-diffraction organization of microclusters as well as the finely dissected kinetics of recruitment and disassociation of molecules from microclusters will be discussed. The role of cell surface molecules in microcluster formation and the kinetics of molecular recruitment via intracellular vesicular trafficking to microclusters is described. Finally, the role of post-translational modifications such as ubiquitination in the downregulation of cell surface signaling molecules is also discussed. These results will be related to the role of these structures and processes in T cell activation.

scholarly journals Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors.

1993 ◽  
Vol 177 (1) ◽  
pp. 219-223 ◽  
Author(s):  
S Wee ◽  
G L Schieven ◽  
J M Kirihara ◽  
T T Tsu ◽  
J A Ledbetter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Intracellular Signaling ◽  
Cell Activation ◽  
Cell Receptor ◽  
Surface Proteins ◽  
Cell Surface Receptors ◽  
Surface Receptors

When T cells are activated via the T cell receptor (TCR) complex a number of cellular substrates, including some cell surface proteins, become phosphorylated on tyrosine (Tyr) residues. Phosphorylation of cytoplasmic Tyr renders these cell surface receptors competent to interact with proteins that link cell surface receptors to protein in the intracellular signaling pathways. Here we show that Tyr residues in the cytoplasmic domain of CD6 become phosphorylated upon T cell activation via the TCR complex. Tyr phosphorylation was observed when the T cells were activated by crosslinking CD3 or by cocrosslinking CD3 with CD2 or CD4, but not when the cells were stimulated by crosslinking CD2, CD4, or CD28 alone. Unlike other Tyr kinase substrates, such as the phospholipase C gamma 1-associated pp35/36 protein, whose level of Tyr phosphorylation is highest when T cells are activated by cocrosslinking CD3 with CD2, the levels of CD6 Tyr phosphorylation are highest when T cells were activated by cocrosslinking CD3 with CD4.

scholarly journals Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 834
Author(s):  
Frederike A. Hartl ◽  
Jatuporn Ngoenkam ◽  
Esmeralda Beck-Garcia ◽  
Liz Cerqueira ◽  
Piyamaporn Wipa ◽  
...  
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Cooperative Interaction ◽  
Tcr Signaling ◽  
Binding Motifs ◽  
Adaptive Immune

The T cell antigen receptor (TCR) is expressed on T cells, which orchestrate adaptive immune responses. It is composed of the ligand-binding clonotypic TCRαβ heterodimer and the non-covalently bound invariant signal-transducing CD3 complex. Among the CD3 subunits, the CD3ε cytoplasmic tail contains binding motifs for the Src family kinase, Lck, and the adaptor protein, Nck. Lck binds to a receptor kinase (RK) motif and Nck binds to a proline-rich sequence (PRS). Both motifs only become accessible upon ligand binding to the TCR and facilitate the recruitment of Lck and Nck independently of phosphorylation of the TCR. Mutations in each of these motifs cause defects in TCR signaling and T cell activation. Here, we investigated the role of Nck in proximal TCR signaling by silencing both Nck isoforms, Nck1 and Nck2. In the absence of Nck, TCR phosphorylation, ZAP70 recruitment, and ZAP70 phosphorylation was impaired. Mechanistically, this is explained by loss of Lck recruitment to the stimulated TCR in cells lacking Nck. Hence, our data uncover a previously unknown cooperative interaction between Lck and Nck to promote optimal TCR signaling.

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