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Summary
This summary is machine-generated.

High-throughput sequencing of T-cell receptor (TCR) clonotypes can track immune responses. This study identified vaccine-associated TCR sequences (VATS) to accurately distinguish vaccinated from naive immune states in mice.

Keywords:
DNA sequencingHLA-A2T cell receptorbiomarkersmonkeypoxvaccinia

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Area of Science:

  • Immunology
  • Bioinformatics
  • Vaccinology

Background:

  • Tracking antigen-specific T-cell responses is challenging due to unknown TCR sequences, sample size limitations, and assay sensitivity.
  • High-throughput sequencing of T-cell receptor (TCR) clonotypes offers a potential method to analyze immunological histories.

Purpose of the Study:

  • To develop a method for identifying and quantifying pathogen-specific TCR sequences.
  • To establish a diagnostic classifier for distinguishing naive from vaccinated immune states using TCR sequence data.

Main Methods:

  • Utilized high-throughput TCR sequencing to build a database of TCRβ sequences from naive and smallpox-vaccinated mice.
  • Computationally identified 315 vaccine-associated TCR sequences (VATS).
  • Trained a diagnostic classifier using VATS to differentiate immune states and confirmed virus responsiveness of VATS via in vitro assays and tetramer sorting.

Main Results:

  • Developed a database of TCRβ sequences from mouse cohorts.
  • Identified 315 vaccine-associated TCR sequences (VATS).
  • Achieved >99% accuracy in distinguishing naive from vaccinated mice up to 9 months post-vaccination using a VATS-trained classifier. VATS were confirmed to be virus-responsive.

Conclusions:

  • High-throughput TCR sequencing and analysis of VATS provide a sensitive platform for identifying pathogen-specific TCR sequences.
  • This approach enables the sensitive identification and quantification of low-frequency pathogen-specific TCR sequences over time.
  • The developed platform advances the study of individual immunological histories and vaccine responses.