Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

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...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
tRNA Activation02:26

tRNA Activation

Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Social status impacts T-cell responses through synapse strength in the prefrontal cortex.

Cell research·2026
Same author

MR1-ligand cross-linking identifies vitamin B6 metabolites as TCR-reactive antigens.

Cell reports methods·2025
Same author

Activation of Epac2 improves Aβ-induced impairment of memory retrieval in an acute model of Alzheimer's disease.

Neuropharmacology·2025
Same author

GluA1-containing AMPA receptors are necessary for sparse memory engram formation.

Neurobiology of learning and memory·2025
Same author

Amyloid-β-Driven Synaptic Deficits Are Mediated by Synaptic Removal of GluA3-Containing AMPA Receptors.

The Journal of neuroscience : the official journal of the Society for Neuroscience·2025
Same author

How Can Early Stress Influence Later Alzheimer's Disease Risk? Possible Mediators and Underlying Mechanisms.

Biological psychiatry·2024

Related Experiment Video

Updated: Jun 15, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

T cell receptor CDR3 loops influence alphabeta pairing.

Istvan Bartok1, Stephen J Holland, Helmut W Kessels

  • 1Department of Immunology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. i.bartok02@imperial.ac.uk

Molecular Immunology
|March 2, 2010
PubMed
Summary

TCR chain pairing is unpredictable, impacting T cell therapies. Modifying the CDR3 region of the T cell receptor beta chain improved pairing, offering a strategy to enhance therapeutic T cell generation.

More Related Videos

CRISPR-Mediated Reorganization of Chromatin Loop Structure
09:20

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

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

Related Experiment Videos

Last Updated: Jun 15, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

CRISPR-Mediated Reorganization of Chromatin Loop Structure
09:20

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

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

Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • T cell receptor (TCR) transfer is a promising strategy for generating antigen-specific T cells for treating infections and cancers.
  • Challenges in TCR transfer include unpredictable alpha-beta chain pairing, leading to auto-reactivity and diluted therapeutic efficacy.
  • The complementarity determining region 3 (CDR3) loops are key drivers of TCR diversity but can also cause structural strain and pairing issues.

Purpose of the Study:

  • To investigate the role of the T cell receptor beta chain's CDR3 region in dictating pairing efficiency with various alpha chains.
  • To determine if modifying the CDR3 region can overcome pairing restrictions and improve TCR repertoire compatibility.

Main Methods:

  • Molecular modeling was used to assess potential steric incompatibilities.
  • The long CDR3 region of the HY-specific T cell receptor C6 beta chain was replaced with a short, artificial CDR3 region.
  • Pairing efficiency was evaluated with endogenous alpha chains.
  • Surface expression and positive selection in retrogenic mice were assessed.

Main Results:

  • The long CDR3 region of the C6 beta chain was identified as a cause of poor pairing with many alpha chains, consistent with molecular modeling.
  • Replacing the C6 beta CDR3 with a shorter, artificial sequence restored efficient pairing with the endogenous alpha chain repertoire.
  • Despite poor pairing and low surface expression, the wild-type C6 beta chain mediated positive selection in retrogenic mice.

Conclusions:

  • The length and composition of the TCR beta CDR3 region significantly influence alpha-beta chain pairing.
  • Engineering the CDR3 region offers a potential strategy to enhance the efficiency and specificity of TCR-based immunotherapies.
  • Further structural and functional studies are warranted to fully understand TCR pairing mechanisms and optimize TCR engineering for therapeutic applications.