A new article from Cell Reports:
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30863-9
The abstract:
The collection of T cell receptors (TCRs) generated by somatic recombination is large but unknown. We generate large TCR repertoire datasets as a resource to facilitate detailed studies of the role of TCR clonotypes and repertoires in health and disease. We estimate the size of individual human recombined and expressed TCRs by sequence analysis and determine the extent of sharing between individual repertoires. Our experiments reveal that each blood sample contains between 5 million and 21 million TCR clonotypes. Three individuals share 8% of TCRβ- or 11% of TCRα-chain clonotypes. Sorting by T cell phenotypes in four individuals shows that 5% of naive CD4+ and 3.5% of naive CD8+ subsets share their TCRβ clonotypes, whereas memory CD4+ and CD8+ subsets share 2.3% and 0.4% of their clonotypes, respectively. We identify the sequences of these shared TCR clonotypes that are of interest for studies of human T cell biology.
I understand only a fraction of the article at this point, but I was particularly interested in this figure:
and the following passage about Figure 2C:
The overlap count among the three experimental repertoires (89,831 common V3DJ clonotypes) ranked higher than the highest overlap count (184 common V3DJ clonotypes) obtained from any of
the 50,000 comparisons of the synthetic repertoires (Figure 2D). When compared against null model repertoires, the high degree of sharing suggests that a strong biological mechanism shapes
individual human TCRb repertoires in a common manner.
Also, this is an interesting paragraph of the discussion section:
Deeper understanding of the particular recombined TCRs that are shared frequently in the
human population could help us in future studies to understand the variability in immune response of diverse subjects to vaccination, infection, or immunotherapy for cancer. Indeed, using computational V(D)J generative models, we found that shared TCR clonotypes have higher probabilities of being generated through somatic recombination than those appearing in a subset of a population. Targeting highly shared TCR clonotypes by identifying the critical peptides that stimulate those TCRs could be an important approach in future research to develop vaccine formulations that are more broadly effective in diverse populations.
