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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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Diversity of Antigen Receptors01:28

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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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Related Experiment Video

Updated: Jan 10, 2026

DNA Tension Probes to Map the Transient Piconewton Receptor Forces by Immune Cells
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DNA Tension Probes to Map the Transient Piconewton Receptor Forces by Immune Cells

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Chimeric Antigen Receptors Transmit Piconewton Forces that are Coupled with T Cell Function.

Rachel M Fitzgerald, Areeba A Hashmi, Anna M Davis

    Biorxiv : the Preprint Server for Biology
    |November 24, 2025
    PubMed
    Summary

    Chimeric antigen receptor (CAR) T cells transmit piconewton (pN) forces to target cancer cells. This CAR-antigen mechanical force can serve as a biomarker for T cell fitness and predict treatment outcomes.

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    In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

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    Area of Science:

    • Immunology
    • Biophysics
    • Cancer Therapy

    Background:

    • Chimeric antigen receptor (CAR) T cells are engineered for cancer immunotherapy.
    • The role of piconewton (pN) forces in T cell receptor (TCR) function is increasingly recognized.
    • The presence and significance of mechanical forces in CAR T cell interactions remain largely unexplored.

    Purpose of the Study:

    • To investigate the mechanical forces transmitted by CAR T cells to their target antigens.
    • To explore the potential of CAR-antigen forces as biomarkers for T cell potency and fitness.
    • To elucidate the molecular mechanisms underlying CAR T cell force generation and transmission.

    Main Methods:

    • Utilized DNA-based tension probes to measure forces between CAR T cells and target antigens.
    • Employed an established CAR T cell exhaustion model to correlate force with cytotoxic capacity.
    • Conducted pharmacological inhibition studies targeting key signaling molecules (actin, Zap70, Src kinases).
    • Performed structural engineering of CAR components to assess their impact on force transmission.

    Main Results:

    • CAR T cells transmit 8-19 pN forces to target antigens on a timescale of ~1 second.
    • CAR-antigen force magnitude is independent of CAR expression level but shows donor heterogeneity.
    • CAR-antigen force strongly correlates with CAR exhaustion and cytotoxic capacity.
    • CAR forces are dependent on actin, Zap70, Src family kinases, and CD3ζ ITAMs.
    • Dasatinib, a tyrosine kinase inhibitor, dose-dependently reduces both CAR-antigen force and function.

    Conclusions:

    • CAR T cells actively transmit piconewton forces to their cognate antigens.
    • CAR-antigen mechanical force is a potential biomarker for T cell fitness, potency, and exhaustion.
    • Understanding CAR mechanics offers insights into CAR T cell design and personalized treatment strategies.
    • These findings highlight the significance of mechanical forces in CAR T cell-mediated immunotherapy.