AI Article Synopsis
- Tracking T cell responses is challenging due to limited knowledge of specific TCR sequences and sample size constraints.
- High-throughput TCR sequencing allows the creation of a database from mouse studies, enabling the identification of 315 vaccine-associated TCR sequences (VATS).
- The VATS library proved efficient in distinguishing between naive and vaccinated samples with over 99% accuracy, paving the way for better detection of pathogen-specific TCR sequences in the future.
Article Abstract
Tracking antigen-specific T cell responses over time within individuals is difficult because of lack of knowledge of antigen-specific TCR sequences, limitations in sample size, and assay sensitivities. We hypothesized that analyses of high-throughput sequencing of TCR clonotypes could provide functional readouts of individuals' immunological histories. Using high-throughput TCR sequencing, we develop a database of TCRβ sequences from large cohorts of mice before (naive) and after smallpox vaccination. We computationally identify 315 vaccine-associated TCR sequences (VATS) that are used to train a diagnostic classifier that distinguishes naive from vaccinated samples in mice up to 9 months post-vaccination with >99% accuracy. We determine that the VATS library contains virus-responsive TCRs by in vitro expansion assays and virus-specific tetramer sorting. These data outline a platform for advancing our capabilities to identify pathogen-specific TCR sequences, which can be used to identify and quantitate low-frequency pathogen-specific TCR sequences in circulation over time with exceptional sensitivity.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770954 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.11.009 | DOI Listing |
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