Deep Sequencing Methods Uncover Diversity in Human TCR Genes

T-cells are a vital component of our immune system, utilizing T-cell receptors (TCRs) to identify foreign invaders and tumor cells. The variability of human TCR genes was previously unknown, making it difficult to understand the wide range of responses to infections and vaccines seen in populations. However, a recent study by researchers at the Karolinska Institutet has shed light on this topic. They examined TCR genes in 45 people from different populations and found that every individual, other than identical twins, has a unique set of TCR gene variants.

The researchers utilized deep sequencing of blood samples and found that these genes vary significantly between individuals and populations. The study also identified 175 new TCR gene variants, doubling the number of known variants at the time of writing. 

The variability in TCR genes cannot be detected using standard whole genome sequencing methods, but with the development of specialized deep sequencing methods and analysis software, the study was able to provide highly precise definitions of B- and T-cell receptor genes. The results also provide new information on how the immune system has developed throughout history, and the researchers are interested in uncovering the function of TCR variants inherited from Neanderthal ancestors.

The new TCR gene database may become an essential tool in developing new therapeutic approaches. “Understanding human genetics is fundamental for the development of targeted treatments,” says Gunilla Karlsson Hedestam, the study’s lead author. The methods described in the study provide new opportunities, especially in the cancer field, where T-cells are central to several promising forms of immunotherapy.

The researchers are now investigating the functional significance of the newly discovered gene variants and how this variation impacts our T-cell responses. They are also planning extended studies involving large groups of individuals to examine the role of TCR gene variation in diseases we know involve T cells, such as infectious diseases, cancer, and autoimmune disorders.

These findings demonstrate remarkable variation in TCR genes in both individuals and populations, providing a strong incentive for including allelic variation in studies of TCR function in human biology.