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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Cytokinesis segregates a cell’s chromosomes and organelles into its daughter cells. Organelles divide and grow prior to cell division but cannot be synthesized de novo; therefore, cells must receive at least one copy of each organelle to survive. Currently, many of the details of how the organelles are distributed are not yet fully elucidated.
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A DNA/Ki67-Based Flow Cytometry Assay for Cell Cycle Analysis of Antigen-Specific CD8 T Cells in Vaccinated Mice
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Asymmetric cell division safeguards memory CD8 T cell development.

Fabienne Gräbnitz1, Dominique Stark1, Danielle Shlesinger2

  • 1Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.

Cell Reports
|May 13, 2023
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Summary
This summary is machine-generated.

Asymmetric cell division (ACD) safeguards memory CD8 T-cell generation during strong T-cell receptor (TCR) stimulation. Inhibiting ACD reduces memory precursor cells, highlighting its crucial role in T-cell differentiation.

Keywords:
CD8 T cell differentiationCD8 T cell memoryCP: Cell biologyCP: ImmunologyT cell receptor signaling strengthasymmetric cell divisionfate diversificationlineage tracingsingle cell tracking

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Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • T-cell receptor (TCR) stimulation strength and asymmetric distribution of fate determinants influence T-cell differentiation.
  • Asymmetric cell division (ACD) is a potential mechanism regulating cell fate.
  • CD8 T-cell memory formation is critical for adaptive immunity.

Purpose of the Study:

  • To investigate the role of asymmetric cell division (ACD) in CD8 T-cell differentiation.
  • To determine if ACD is specifically involved in memory CD8 T-cell generation.
  • To elucidate the impact of TCR stimulation strength on ACD and T-cell fate.

Main Methods:

  • Live imaging of T-cells undergoing division.
  • Analysis of single-cell-derived colonies.
  • Pharmacological inhibition of protein kinase Cζ (PKCζ) to block ACD.
  • Varying T-cell receptor (TCR) stimulation strength (strong vs. weak).

Main Results:

  • Strong TCR stimulation significantly increases ACD rates in CD8 T-cells.
  • ACD during the first mitosis correlates positively with the generation of memory precursor cells.
  • Inhibition of ACD via PKCζ blockade during strong TCR stimulation markedly reduces memory precursor cell formation.
  • ACD does not influence T-cell fate commitment under weak TCR stimulation conditions.

Conclusions:

  • Asymmetric cell division (ACD) acts as a crucial safeguard mechanism for generating memory CD8 T-cells, particularly under strong TCR stimulation.
  • The extent of ACD in the first mitosis directly impacts the pool of memory precursor cells.
  • ACD's role in T-cell fate regulation is dependent on the strength of the initial TCR signal, providing mechanistic insights into CD8 T-cell differentiation.