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Updated: Jan 19, 2026

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
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MATE-Seq: microfluidic antigen-TCR engagement sequencing.

Alphonsus H C Ng1, Songming Peng, Alexander M Xu

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd, Pasadena, CA 91125, USA.

Lab on a Chip
|September 11, 2019
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Summary
This summary is machine-generated.

This study introduces a novel method to identify T cell receptor (TCR) genes targeting specific peptide antigens. The technique enhances sensitivity for detecting antigen-specific TCRs, aiding therapeutic development.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Biotechnology

Background:

  • Adaptive immunity relies on T cell receptors (TCRs) recognizing peptide antigens.
  • Identifying TCRs specific to pathogens or mutated proteins is crucial for immunotherapy.

Purpose of the Study:

  • To develop a method for selective labeling, isolation, and TCR gene sequencing of peptide antigen-specific CD8+ T cells.
  • To preserve the link between the recognized peptide and the TCR gene sequence.

Main Methods:

  • Utilized magnetic nanoparticles functionalized with peptide-MHC tetramers to label antigen-specific CD8+ T cells.
  • Employed an integrated microfluidic device for cell isolation and on-chip sorting.
  • Directly amplified TCR genes for sequencing, preserving peptide recognition information.

Main Results:

  • Achieved a 1000-fold sensitivity enhancement for detecting antigen-specific TCRs compared to bulk analysis.
  • Demonstrated simultaneous capture of two virus antigen-specific TCRs from a T cell population.
  • The platform requires minimal input (approx. 100,000 CD8+ T cells) and allows multiplexed analysis.

Conclusions:

  • The developed platform enables efficient identification of peptide antigen-specific TCRs.
  • This method advances the discovery of TCRs for therapeutic applications in infections and cancer.
  • The technology offers high sensitivity, low cell input, and multiplexing capabilities for TCR repertoire analysis.