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T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

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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Related Experiment Video

Updated: Nov 5, 2025

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

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

Published on: April 25, 2018

Quantifying persistence in the T-cell signaling network using an optically controllable antigen receptor.

Michael J Harris¹, Muna Fuyal², John R James^1,2

¹Molecular Immunity Unit, Department of Medicine, MRC-LMB, University of Cambridge, Cambridge, UK.

Molecular Systems Biology

|May 14, 2021

Summary

T cells integrate gene expression outputs, not discrete signals, due to rapid signal dissipation (~15 min). This finding enhances chimeric antigen receptor (CAR)-T cell therapy through optimized pulsatile stimulation.

Keywords:

T cells cell signaling optogenetics receptors transcription factors

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Last Updated: Nov 5, 2025

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

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Published on: April 25, 2018

Real-time Live Imaging of T-cell Signaling Complex Formation

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Published on: June 23, 2013

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay

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Published on: October 30, 2015

Area of Science:

Immunology
Cellular Biology
Biophysics

Background:

T cells mount immune responses by sensing antigen-presenting cells.
It is hypothesized that T cells integrate signals from multiple interactions for a potent response.
Understanding T cell signaling dynamics is crucial for immunotherapy.

Purpose of the Study:

To quantify the capacity of T cells to integrate stimuli.
To investigate the persistence of intracellular T cell signaling.
To engineer optical control for enhanced chimeric antigen receptor (CAR)-T cell therapy.

Main Methods:

Developed an optically tunable antigen receptor in cell conjugates.
Controlled duration and intensity of intracellular T cell signaling.
Engineered optical control into a clinically relevant CAR.

Main Results:

T cell intracellular signals dissipate within ~15 minutes upon disruption of receptor input.
Sustained proximal receptor signaling is essential for maintaining gene transcription.
Pulsatile stimulation increased CAR-T cell activation threefold by exploiting limited signal persistence.

Conclusions:

T cells primarily accumulate gene expression outputs rather than integrate discrete intracellular signals.
Limited signal persistence in T cells can be therapeutically exploited.
Findings offer insights into cellular network signaling dynamics and CAR-T cell optimization.