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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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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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B Cell Activation and Differentiation01:24

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

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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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T Cell Types and Functions01:24

T Cell Types and Functions

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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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Related Experiment Video

Updated: May 25, 2025

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
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Memory CD4+ T cells sequentially restructure their 3D genome during stepwise activation.

Alexander I Ward1, Jose I de Las Heras2, Eric C Schirmer2

  • 1Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, United Kingdom.

Frontiers in Cell and Developmental Biology
|February 28, 2025
PubMed
Summary
This summary is machine-generated.

Memory CD4+ T cells exhibit dynamic 3D chromatin architecture changes in response to stimulation. These structural shifts, driven by cytokines and co-receptors, prime cells for gene expression responses.

Keywords:
3D-genome organizationHi-CIL-2enhancer–promoter interactionsgene expression regulationmemory CD4+ T cellsprimed/de-primed genessequential immune activation

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Area of Science:

  • Immunology
  • Genomics
  • Epigenetics

Background:

  • CD4+ T cells possess transcriptomic plasticity enabling transitions between activated and memory states.
  • Understanding how chromatin structure (1D and 3D) supports this plasticity is crucial.

Purpose of the Study:

  • To evaluate a commercial Hi-C kit for primary immune cells.
  • To investigate 3D chromatin architecture dynamics in memory CD4+ T cells.
  • To correlate chromatin changes with gene expression under varying stimulation conditions.

Main Methods:

  • Utilized an in situ Hi-C kit with varying numbers of memory CD4+ T cells.
  • Generated Hi-C and RNA-seq libraries from stimulated and unstimulated primary T cells.
  • Applied different stimulation conditions: IL-2 alone, and combined TCR/CD28/IL-2 stimulation.

Main Results:

  • Achieved comparable Hi-C contact matrices across different cell input numbers.
  • Observed dynamic changes in 3D genome organization, including topologically associated domains (TADs).
  • Found that IL-2 stimulation induced significant genome organization changes, further enhanced by TCR/CD28 co-stimulation.

Conclusions:

  • 3D chromatin architecture in memory CD4+ T cells is highly dynamic and responsive to stimuli.
  • Stimuli induce sequential changes in 3D architecture, potentially priming cells for gene expression.
  • TADs are not invariant but undergo dynamic alterations during T cell activation.