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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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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MAPK Signaling Cascades01:07

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Mitogens and the Cell Cycle02:38

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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T Cell Types and Functions01:24

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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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cAMP-dependent Protein Kinase Pathways01:25

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Related Experiment Video

Updated: Jan 15, 2026

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
07:48

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist

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Antigen affinity modulates ERK pulsing frequency during T cell activation.

Vera-Marie E Dunlock1, Sergi Regot1

  • 1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Science Signaling
|January 13, 2026
PubMed
Summary
This summary is machine-generated.

T cell antigen discrimination relies on signaling timing. Intermediate-affinity antigens cause pulsatile extracellular signal-regulated kinase (ERK) activity, with T cell activation linked to cumulative ERK signaling, revealing insights into T cell receptor dynamics.

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Area of Science:

  • Immunology
  • Cellular Signaling
  • Biophysics

Background:

  • T cell antigen discrimination is crucial for adaptive immunity.
  • T cell receptor (TCR) interaction stability with antigens dictates T cell responses.
  • Understanding the temporal dynamics of TCR signaling is key to T cell activation.

Purpose of the Study:

  • To investigate extracellular signal-regulated kinase (ERK) signaling dynamics in T cells in real-time.
  • To correlate ERK signaling patterns with antigen affinity and T cell activation.
  • To elucidate the molecular mechanisms governing TCR-induced ERK signaling.

Main Methods:

  • Real-time, single-cell imaging of TCR-antigen interactions.
  • Controlled experimental system to vary antigen affinity.
  • Analysis of ERK signaling dynamics, including frequency and amplitude.
  • Investigating the roles of LCK, MEK, MLKs, RAFs, and LAT in signaling.

Main Results:

  • Intermediate-affinity antigens induced pulsatile ERK activity at varying frequencies.
  • T cell activation correlated with the cumulative amount of ERK signaling.
  • ERK pulsing frequency was dependent on LCK activity, while MEK modulated amplitude.
  • MLKs and RAFs differentially regulated upstream signaling condensates involving LAT.

Conclusions:

  • TCR signaling exhibits complex spatiotemporal dynamics crucial for T cell activation.
  • ERK signaling frequency and amplitude are precisely controlled by upstream kinases.
  • Distinct roles of MLKs and RAFs in organizing signaling complexes highlight regulatory mechanisms.