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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

714
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...
714

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Related Experiment Video

Updated: Jun 27, 2025

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

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Structure-Based Rational and General Strategy for Stabilizing Single-Chain T-Cell Receptors to Enhance Affinity.

Jia-Ling Zou1, Kai-Xiang Chen2, Xiao-Juan Wang2

  • 1Lab of Computational Chemistry and Drug Design, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Journal of Medicinal Chemistry
|April 25, 2024
PubMed
Summary
This summary is machine-generated.

Engineered single-chain T-cell receptors (scTCRs) show improved stability and solubility. This advancement facilitates the development of T-cell receptor therapeutics with enhanced affinity and retained specificity.

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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
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Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
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Area of Science:

  • Immunology
  • Biochemistry
  • Structural Biology

Background:

  • The T-cell receptor (TCR) is essential for cellular immunity.
  • Single-chain TCRs (scTCRs) offer therapeutic advantages by preventing T-cell receptor mispairing.
  • scTCRs face challenges in stability and solubility, hindering their application.

Purpose of the Study:

  • To identify conserved structural motifs in variable TCR domains.
  • To develop a general strategy for stabilizing scTCRs.
  • To engineer scTCRs with improved stability and retained binding affinity.

Main Methods:

  • Identification of conserved structural motifs across germlines and species.
  • Theoretical analysis to pinpoint destabilizing factors.
  • Residue substitution at specific IMGT positions based on germline consensus sequences.

Main Results:

  • A general strategy for stabilizing scTCRs was established.
  • Engineered scTCRs demonstrated enhanced stability and solubility.
  • Optimized scTCRs maintained binding affinities comparable to native αβ-TCRs (μM to pM range).

Conclusions:

  • The developed scTCR engineering strategy effectively enhances stability and solubility.
  • This approach yields affinity-enhanced and specificity-retained scTCR formats.
  • These findings significantly contribute to advancing TCR-based therapeutics development.