| First Author | Wolf K | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 9 | Pages | 2369-2378.e4 |
| PubMed ID | 30485806 | Mgi Jnum | J:270872 |
| Mgi Id | MGI:6278329 | Doi | 10.1016/j.celrep.2018.11.009 |
| Citation | Wolf K, et al. (2018) Identifying and Tracking Low-Frequency Virus-Specific TCR Clonotypes Using High-Throughput Sequencing. Cell Rep 25(9):2369-2378.e4 |
| abstractText | 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 TCRbeta 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. |
