A groundbreaking technique developed by researchers at St. Jude Children’s Research Hospital has transformed the analysis of T cells, immune cells crucial for combating infections and cancers. This new method, known as Throughput-Intensive Rapid TCR Library sequencing (TIRTL-seq), offers a comprehensive view of an individual’s entire T-cell repertoire at a fraction of the cost compared to existing techniques. Published in Nature Methods, this study presents a significant advancement in immunological research, addressing critical limitations in the field.
The conventional methods for T-cell analysis have been both costly and impractical. Traditionally, researchers could only analyze approximately 20,000 T cells at a time, spending around $2,000 for each analysis. In contrast, TIRTL-seq can process up to 30 million T cells in a single run for just $200. This dramatic reduction in cost and increase in capacity allows more scientists to engage in T-cell research, potentially accelerating discoveries in immunology.
Revolutionizing T-Cell Research
Dr. Victor Torres, chair of the St. Jude Department of Host-Microbe Interactions, emphasizes the democratizing effect of this new technology: “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.” This innovation could lead to significant advancements in understanding immune responses and developing new treatments for various diseases, including cancers and infectious diseases.
The TIRTL-seq method employs a combination of physical automation, streamlined computational processing, and improved laboratory techniques. By dividing full samples into numerous subsamples, the technique utilizes statistical methods to enhance sequencing accuracy and pairing results. This approach enables researchers to process a much larger number of cells while improving the overall quality of the data obtained.
In a demonstration of TIRTL-seq’s capabilities, the research team explored immune responses to SARS-CoV-2, the virus responsible for COVID-19. They utilized blood samples from the St. Jude Tracking Study of Immune Responses Associated with COVID-19, a clinical trial established in 2020. The method successfully tracked changes in T-cell receptors before and after infection, revealing patterns that were previously difficult to identify. Notably, TIRTL-seq uncovered a previously undetected Epstein-Barr virus infection, suggesting its potential as a diagnostic tool.
Accessibility and Future Implications
The researchers have made TIRTL-seq freely available online, including detailed instructions for implementation. This decision reflects a commitment to fostering collaboration and innovation within the scientific community. Dr. Torres stated, “TIRTL-seq is the first technology to provide a full picture of people’s T-cell receptors at scale. 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 was co-authored by Mikhail Pogorelyy and Allison Kirk, along with several other contributors, and supported by grants from the National Institute of Allergy and Infectious Diseases and other organizations. As researchers continue to utilize TIRTL-seq, its implications for advancing T-cell science and improving healthcare outcomes for patients are substantial.
The developments at St. Jude Children’s Research Hospital mark a pivotal moment in the pursuit of understanding the immune system and pave the way for enhanced diagnostic and therapeutic strategies in the fight against severe diseases.
