The diversity and complexity of immune receptors poses a challenge to our understanding of the physical principles that control certain properties of biological systems, such as recognition. Support to the RECOGNIZE (Physical principles of recognition in the immune system) project has fed into recent findings that shine some light on the structure and overlap of adult human T cell receptor repertoires. Researchers suggest that, during pregnancy, twin embryos may exchange T cells through cord blood and that T cell clones produced before birth may persist in the body of a person for about 40 years.
Immune systems – diverse, complex and vital
The immune system can respond to a multitude of different pathogens because of the diverse range of T-cell receptors (TCRs) present in the body. However, the TCRs present on the surface of one T cell are usually all identical. The set of cells with the same TCR defines a T-cell clonotype, and the set of T-cells in the body can be thought of as a repertoire of clonotypes. Understanding how this diversity is generated, and its evolution through age, is essential to our knowledge of adaptive immunity.
From individual to individual these receptors differ, however, it is known that some of the same receptors appear in people regardless of whether they are related or not. This shared pool, known as ‘the public repertoire’, is often thought to be due to our immune systems evolving in response to common antigenic challenges, although other reasons have been proposed.
In a study
recently published in ‘Computational Biology’, researchers set out how their statistical analysis of deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, shows that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age.
The study considers that if this shared repertoire is not invariably due to common challenges, then how can it be explained? It proposes that a sizeable fraction of the public repertoire is created before birth. Part of the study examined the sharing of repertoires between three sets of identical twins and resulting observations support the idea that the existence of shared sequences goes beyond coincidence in twins.
The teams writes, ‘(…) our general framework for analysing the overlap between different repertoires has far-reaching practical implications for the tracking of T-cell clonotypes in the clinic. In particular, the analysis of overlap between pre- and post-treatment repertoires using probabilistic characteristics of clonotypes sharing could help determine the host or donor origin of clonotypes after hematopoietic stem cell transplantation (HSCT), and also increase reliability of malignant clones identification in minimal residual disease follow-up. ‘
For more information, please see: CORDIS project web page