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Related Concept Videos

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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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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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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CD28 and TCR differentially impact naïve and memory T cell responses.

Cayman Williams1, Dalisay Giovacchini1, Alan Kennedy1

  • 1UCL Institute of Immunity and Transplantation, Division of Infection and Immunity, London, NW3 2PP, UK.

Discovery Immunology
|June 11, 2025
PubMed
Summary

CD28 co-stimulation impacts T cell division differently based on its quantity and intensity relative to T cell receptor (TCR) signals. These findings reveal distinct roles for CD28 and TCR in naïve and memory T cell responses.

Keywords:
CD28T cellT cell memoryT cell receptorco-stimulation

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Area of Science:

  • Immunology
  • Cellular Biology

Background:

  • CD28 co-stimulation is crucial for anti-tumour immunity and autoimmune disease treatment.
  • CD28 modulates T cell activation thresholds but its interaction with T cell receptor (TCR) signaling is complex and varies across T cell subsets.

Purpose of the Study:

  • To investigate the distinct contributions of CD28 co-stimulation and TCR signaling in human CD4+ T cell responses.
  • To elucidate how the quantity and relative intensity of CD28 co-stimulation impact T cell division and function.

Main Methods:

  • Utilized in vitro stimulation assays to analyze human CD4+ T cell responses.
  • Compared the effects of varying CD28 co-stimulation levels relative to TCR signaling.

Main Results:

  • Both the quantity and relative intensity of CD28 co-stimulation, compared to TCR signals, differentially affect naïve and memory T cell division.
  • CD28 co-stimulation demonstrated TCR-independent effects on memory T cell phenotype and cytokine production.
  • In certain contexts, CD28 co-stimulation was observed to antagonize TCR-driven T cell functions.

Conclusions:

  • The interplay between CD28 co-stimulation and TCR signaling is intricate and context-dependent.
  • Naïve and memory T cells exhibit distinct utilization patterns of CD28 and TCR signals for activation and function.