Deciphering the TCR Repertoire

TCR Repertoire

Between the 4th and 19th centuries AD, knowledge of how to read and write Egyptian hieroglyphs was essentially nonexistent. Not until 1799 when French officers found the Rosetta Stone, was there any hope to translate this complex script. With the help of the stone, scholars were able to crack the complex code of hieroglyphics, and gain a deeper understanding of ancient Egyptian life. 

Just like the Rosetta Stone was critical to understanding ancient Egyptian mysteries, the immune repertoire is key to unlocking insights about an individual’s immune response to their environment. Thankfully, advances in next-generation sequencing and computational biology have made translating the immune repertoire a modern reality. 

What is the immune repertoire and why is it important? 

Specialized cells of the immune system, such as macrophages, T-cells, and B-cells, work together to identify threats in the body, and activate a coordinated and complex immune response. An important part of the immune response occurs when a T-cell detects a threatening target and receptors on the T-cell bind to the enemy cell, or antigen. The T-cells then duplicate many times in a process called clonal expansion, and remain in the body to quickly respond when the same antigen appears again.  

Each unique receptor on the T-cell recognizes only a single antigen, and this range is encoded by a fixed number of gene segments. Thus, the T-cell receptor (TCR) repertoire holds the key to understanding the diversity of the immune system and how it responds to disease-causing antigens. By sequencing the TCR repertoire and learning the genetic code of the cells, researchers can begin to understand which antigens those particular T-cells have targeted, build a disease profile that an individual has encountered, and determine whether a particular vaccine or immunotherapy drug may be effective. This powerful information can be used to develop diagnostic tests, create therapeutic products, and predict responses to immunotherapies. 

This week, immune profiling company, MIODx launched ClonoMapTM Immune Profiler, an analysis and biomarker discovery platform that allows researchers to probe the immune system and better understand how an individual’s T-cells can make them susceptible to disease or certain therapies, and how that can change over time. 

A healthy individual’s immune system consists of a vast TCR repertoire, in the order of 109 cells, so the ability to scale up computational resources is crucial. Powered by the scalable and flexible DNAnexus Titan Platform, ClonoMapTM Immune Profiler enables researchers to conduct powerful analysis by incorporating large datasets from multiple and longitudinal studies, integrating metadata, and processing multiple versions of analysis in parallel to generate and test hypotheses on the relevance of TCR samples as biomarkers. 

The MIODx team is at the cutting edge of TCR repertoire research. By empowering researchers with the analytical tools to study the genetic code of T-cells, gain an understanding of the antigens that the T-cells target, and study how the immune system changes over the course of an individual’s lifetime, MIODx is laying the groundwork to translate the TCR repertoire into actionable insights to inform human health. 

Read more about MIODx and their ClonoMapTM Immune Profiler here.