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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

Diversity of Antigen Receptors

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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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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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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.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Autologous T Cell Antigen Coupler Targeting HER2 (TAC01-HER2) in Advanced or Metastatic Solid Tumors.

Annals of oncology : official journal of the European Society for Medical Oncology·2026
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Preclinical Development of T Cells Engineered to Express a T-Cell Antigen Coupler Targeting Claudin 18.2-Positive Solid Tumors.

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Related Experiment Video

Updated: May 25, 2025

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

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Tuning TCR complex recruitment to the T cell antigen coupler (TAC) enhances TAC-T cell function.

Trevor M Morey1, Tania Benatar2, Stacey X Xu2

  • 1Department of Biochemistry, University of Toronto, 661 University Avenue, MaRS Centre, West Tower, Room 1612, Toronto, ON, M5G 1M1, Canada.

Scientific Reports
|February 25, 2025
PubMed
Summary
This summary is machine-generated.

Optimizing T cell antigen coupler (TAC) receptors is key for effective cancer immunotherapy. Lower TCR affinities with fast off-rates enhance in vivo functionality, improving anti-tumor immunity.

Keywords:
Binding affinityCancerT cell antigen coupler (TAC)T cell receptor (TCR)T cell therapyUCHT1scFv

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A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
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Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
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A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
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Area of Science:

  • Immunology
  • Biotechnology
  • Oncology

Background:

  • T cell antigen coupler (TAC) receptors are synthetic receptors designed to enhance T cell-based cancer therapies.
  • TACs aim to provide safe, long-lasting anti-tumor immunity by recapitulating natural T cell receptor (TCR) signaling.
  • Unlike other designs, TAC technology separates antigen binding from TCR/CD3 complex recruitment.

Purpose of the Study:

  • To investigate the impact of single amino-acid changes in the TAC domain on TCR recruitment.
  • To analyze the biophysical properties and in vivo functionality of Claudin 18.2-directed TAC receptors.
  • To determine the optimal balance of TCR affinity and off-rates for effective TAC T cell receptor design.

Main Methods:

  • Engineered Claudin 18.2-directed TAC receptors with specific amino-acid alterations in the TCR recruitment domain.
  • Evaluated in vivo functionality of modified TAC receptors in preclinical solid tumor models.
  • Assessed biophysical properties, including TCR affinities and off-rates, of different TAC receptor constructs.

Main Results:

  • Single amino-acid changes in the TAC domain significantly enhanced in vivo functionality.
  • TAC receptors with high TCR affinities were suboptimal for anti-tumor activity.
  • Receptor constructs with lower TCR affinities and fast off-rates demonstrated improved functionality.

Conclusions:

  • Balancing TCR recruitment affinity and off-rates is critical for designing effective TAC T cell receptors.
  • This optimization principle may extend to other therapeutic strategies involving TCR signaling.
  • Fine-tuning TAC receptor design can enhance T cell-mediated anti-tumor immunity.