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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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...
T Cell Activation and Clonal Selection01:22

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...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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...
T Cell Types and Functions01:24

T Cell Types and Functions

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...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview

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Related Experiment Video

Updated: May 31, 2026

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
08:48

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain

Published on: October 25, 2016

Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains.

D H Aggen1, A S Chervin, T M Schmitt

  • 1Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.

Gene Therapy
|July 15, 2011
PubMed
Summary
This summary is machine-generated.

Engineered T-cell receptors (TCRs) can fight cancer but risk dangerous mispairing. A novel single-chain TCR (scTv) strategy completely prevents mispairing, enabling safer adoptive T-cell therapies.

More Related Videos

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
11:21

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs

Published on: September 10, 2017

Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice
09:08

Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice

Published on: July 11, 2016

Related Experiment Videos

Last Updated: May 31, 2026

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
08:48

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain

Published on: October 25, 2016

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
11:21

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs

Published on: September 10, 2017

Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice
09:08

Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice

Published on: July 11, 2016

Area of Science:

  • Immunology
  • Cell Therapy
  • Molecular Engineering

Background:

  • Adoptive T-cell therapy using exogenous T-cell receptor (TCR) genes shows promise for cancer and viral diseases.
  • A significant challenge is the mispairing of exogenous and endogenous TCR chains, leading to graft-versus-host reactions.
  • Current engineering methods to reduce mispairing, like cysteine modification, are insufficient.

Purpose of the Study:

  • To develop a T-cell receptor (TCR) engineering strategy that completely prevents mispairing with endogenous TCRs.
  • To create a functional T-cell therapy that avoids graft-versus-host reactions caused by TCR mispairing.
  • To investigate the potential of a single-chain TCR (scTv) approach for safer adoptive T-cell therapies.

Main Methods:

  • Engineering exogenous TCR constant regions with cysteine to promote proper pairing.
  • Developing a stabilized Vα/Vβ single-chain TCR (scTv) by deleting constant regions.
  • Linking high-affinity scTv to intracellular signaling domains (Lck, CD28) for T-cell activation.
  • Assessing T-cell responses in the absence of CD3 subunits and co-receptors.

Main Results:

  • Cysteine engineering reduced but did not eliminate mixed heterodimer formation.
  • Deletion of TCR constant regions to create scTv completely avoided mispairing.
  • scTv, linked to signaling domains, activated T cells independently of CD3 subunits.
  • Transduced T cells responded to target antigens without acquiring new specificities.

Conclusions:

  • Single-chain TCR (scTv) technology offers a complete solution to TCR mispairing in adoptive T-cell therapy.
  • This approach enhances the safety profile of T-cell therapies by preventing graft-versus-host reactions.
  • scTv-based T-cell therapies can be engineered for targeted antigen recognition and activation, independent of endogenous TCR signaling pathways.