A groundbreaking technique developed at St. Jude Children’s Research Hospital is set to transform the analysis of T cells, the immune system’s key players in combating infections and cancers. The new method, known as Throughput-Intensive Rapid TCR Library sequencing (TIRTL-seq), significantly reduces the cost and complexity of T-cell analysis, making it more accessible for scientists worldwide.
Current methods for studying T-cell receptors, which are essential for recognizing threats to the body, can be financially burdensome and logistically challenging. Traditional techniques require the processing of millions of T cells, often costing approximately $2,000 to analyze just 20,000 cells. In contrast, TIRTL-seq allows researchers to analyze up to 10 million T cells in a single run for only $200. This advancement was detailed in a study published in Nature Methods.
Enhanced Capabilities and Efficiency
The TIRTL-seq technique outperforms existing methods by processing a staggering 30 million T cells simultaneously, vastly exceeding the capacity of current practices, which are limited to about 20,000 cells. This breakthrough stems from a combination of physical automation, streamlined computational processing, and refined laboratory techniques that enhance the accuracy of T-cell receptor pairing.
Dr. Victor Torres, chair of the Department of Host-Microbe Interactions at St. Jude and overseer of the TIRTL-seq initiative, emphasized the democratization of immune research that this technology facilitates. “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,” he stated.
The introduction of TIRTL-seq comes as part of an ongoing effort by St. Jude to decode the complexities of individual T-cell repertoires—critical for understanding variations in immune responses. This initiative, launched in 2023, aims to apply insights from T-cell analysis to address severe childhood illnesses.
Potential for Future Diagnostics
In a demonstration of TIRTL-seq’s capabilities, 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 proved effective in documenting changes in T-cell receptors before and after infection with the SARS-CoV-2 virus. Notably, TIRTL-seq also identified a previously undetected infection with the Epstein-Barr virus, suggesting its potential utility as a diagnostic tool.
The method has been made freely available online, complete with detailed instructions for implementation. “TIRTL-seq is the first technology to provide a full picture of people’s T-cell receptors at scale,” Torres remarked. “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 study, which includes contributions from co-first authors Mikhail Pogorelyy and Allison Kirk, along with the corresponding author Paul Thomas, received funding from various sources, including the National Institute of Allergy and Infectious Diseases and the American Lebanese Syrian Associated Charities (ALSAC).
As researchers continue to explore the implications of TIRTL-seq, the method stands poised to enhance our understanding of the immune system and facilitate more effective treatments for diseases that affect countless individuals.
