A groundbreaking technique developed by researchers at St. Jude Children’s Research Hospital has significantly advanced the analysis of T cells, the immune cells vital for combating infections and cancers. This innovative method, called Throughput-Intensive Rapid TCR Library sequencing (TIRTL-seq), offers a more comprehensive view of a person’s T-cell repertoire while drastically reducing costs.
Traditionally, analyzing T cells has been both expensive and logistically challenging, often requiring the examination of millions of cells and the precise detection of T-cell receptor pairings. The conventional approach can cost approximately $2,000 to process 20,000 cells, necessitating multiple runs to achieve adequate results. In contrast, TIRTL-seq can analyze up to 10 million T cells in a single run for just $200, making this technique not only more efficient but also accessible to a broader range of researchers.
Revolutionizing T-Cell Research
The findings from this study were published in the prestigious journal Nature Methods. The researchers demonstrated that TIRTL-seq could accurately process up to 30 million T cells at once, far surpassing the maximum capacity of existing technologies, which is limited to around 20,000.
Victor Torres, PhD, chair of the St. Jude Department of Host-Microbe Interactions, emphasized the significance of this advancement: “We have democratized access to understanding immune memory. TIRTL-seq can perform a highly detailed analysis of many T-cell receptors at a cost that makes these experiments feasible for more scientists than ever before, which we hope will push T-cell science forward.”
Understanding the diversity of T-cell receptors present within an individual—referred to as their T-cell repertoire—can elucidate differences in immune responses. In 2023, St. Jude initiated the TIRTL project to enhance the efficiency of T-cell receptor sequencing. The resulting TIRTL-seq method combines physical automation with improved laboratory techniques and streamlined computational processing to optimize both costs and throughput.
Potential for Diagnostic Applications
As a demonstration of TIRTL-seq’s capabilities, the researchers utilized blood samples from the St. Jude Tracking Study of Immune Responses Associated with COVID-19 (SJTRC), a clinical trial initiated during the pandemic. The technique successfully tracked changes in T-cell receptors in individuals before and after infection with SARS-CoV-2. Notably, TIRTL-seq also identified a previously undetected Epstein-Barr virus infection, suggesting its potential as a diagnostic tool in future applications.
The study’s co-first authors, Mikhail Pogorelyy and Allison Kirk, alongside corresponding author Paul Thomas, highlighted the transformative nature of TIRTL-seq. “TIRTL-seq is the first technology to provide a full picture of people’s T-cell receptors at scale,” Torres added. “We’re just beginning to use it to better understand how the immune system works, and how we can adopt those findings into new and better treatments for catastrophic diseases like cancer and infections.”
The research received funding from several organizations, including the National Institute of Allergy and Infectious Diseases and the American Lebanese Syrian Associated Charities (ALSAC). St. Jude has made the TIRTL-seq method publicly accessible, providing step-by-step instructions for implementation in research settings.
As scientists continue to explore the intricacies of the immune system, TIRTL-seq stands out as a pivotal development that promises to enhance our understanding of T-cell functionality and its implications for health and disease.
