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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
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Published on: April 25, 2018

Role of diacylglycerol kinases in T cell development and function

Sruti Krishna1, Xiaoping Zhong

  • 1Department of Pediatrics, Division of Allergy and Immunology and Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

Critical Reviews in Immunology
|April 16, 2013
PubMed

Insights

Diacylglycerol (DAG) kinases (DGKs) regulate T cell development and function by controlling DAG signals. DGK isoforms α and ζ are crucial for T cell tolerance, activation, and responses to viruses and tumors.

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • Diacylglycerol (DAG) is a key second messenger in T cell signaling, generated by phospholipase Cγ1 upon T cell receptor engagement.
  • DAG kinases (DGKs) phosphorylate DAG to phosphatidic acid, terminating DAG-mediated signals and acting as a crucial regulatory brake.
  • Two prominent DGK isoforms, α and ζ, are expressed in T cells and play significant roles in T cell development and function.

Purpose of the Study:

  • To review the diverse roles of Diacylglycerol (DAG) kinases (DGKs) in T cell biology.
  • To highlight recent advancements in understanding DGK function in T cell development, activation, and immune responses.
  • To emphasize the importance of DGK activity in maintaining self-tolerance and regulating immune cell behavior.

Main Methods:

  • This review synthesizes findings from various studies investigating DGK function in T cells.
  • It integrates research on DGK isoforms α and ζ, their signaling pathways, and their impact on T cell development and mature T cell functions.
  • The review incorporates recent discoveries regarding DGK activity at the immune synapse and its role in cellular processes like secretion and adhesion.

Main Results:

  • DGK isoforms α and ζ synergistically regulate the development of both conventional αβ T cells and invariant natural killer T cells.
  • In mature T cells, DGK activity is essential for maintaining self-tolerance by preventing hyperactivation and promoting anergy.
  • Reduced DGK activity in CD8 cells correlates with enhanced responses against viral infections and tumors.

Conclusions:

  • DGK activity is indispensable for proper T cell development, function, and immune homeostasis.
  • Recent research has uncovered novel roles for DGKs in immune synapse dynamics, directional secretion, and T cell adhesion.
  • Further investigation into DGK function promises to yield new insights into T cell-mediated immunity and potential therapeutic strategies.

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