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T Cell Activation and Clonal Selection01:22

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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.
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Precise T cell recognition programs designed by transcriptionally linking multiple receptors.

Jasper Z Williams1,2,3, Greg M Allen1,2,3,4, Devan Shah1,2,3

  • 1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.

Science (New York, N.Y.)
|November 27, 2020
PubMed
Summary
This summary is machine-generated.

Engineered T cells precisely recognize target cells by integrating multiple antigen signals using synthetic Notch receptors. This multireceptor system achieves selective tumor targeting, demonstrating advanced cellular recognition capabilities.

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Area of Science:

  • Synthetic biology
  • Cellular engineering
  • Immunology

Background:

  • Cellular recognition relies on integrating signals from multiple receptors for accuracy.
  • Individual molecular interactions often lack the precision for complex biological recognition tasks.
  • Synthetic biology offers tools to engineer novel cellular functions.

Purpose of the Study:

  • To engineer multireceptor cell-cell recognition circuits using synthetic Notch receptors.
  • To enable engineered T cells to integrate multiple antigen recognition events.
  • To achieve precise and robust cellular recognition with tunable logic.

Main Methods:

  • Designed a library of synthetic Notch receptors to create transcriptional interconnections.
  • Integrated extra- and intracellular antigen recognition pathways.
  • Implemented positive and negative logic gates for antigen integration.
  • Tested a three-antigen AND gate circuit in vivo for tumor targeting.

Main Results:

  • Developed synthetic circuits capable of integrating up to three different antigens.
  • Demonstrated robustness to cellular heterogeneity.
  • Engineered T cells exhibited precise recognition based on integrated antigen signals.
  • A three-antigen AND gate selectively cleared three-antigen tumors in vivo, sparing two-antigen tumors.

Conclusions:

  • Synthetic Notch receptor-based circuits enable sophisticated, multireceptor-mediated cell-cell recognition.
  • Daisy-chaining molecular recognition events is a powerful strategy for engineering cellular behavior.
  • This approach enhances specificity and precision in engineered cell therapies, particularly for cancer treatment.