Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.27.223354v1?rss=1

Authors: Quiniou, V., Barennes, P., Martina, F., Mhanna, V., Vantomme, H., Pham, H. P., Shugay, M., Six, A., Mariotti-Ferrandiz, E., Klatzmann, D.

Abstract:

T cell receptors (TCRs) are formed by stochastic gene rearrangements, theoretically generating >>1019 sequences. They are selected during thymopoiesis, which releases a repertoire of about 108 unique TCRs per individual. How evolution shaped a process that produces TCRs that would effectively respond to infectious agents is a central question of immunology. The paradigm is that a diverse enough repertoire of TCRs should always provide a proper, though rare, specificity for any given need. Expansion of such rare T cells would provide enough fighters for an efficacious immune response and enough antigen-experienced cells for memory. We show here that thymopoiesis releases a large population of CD8+ T cells harbouring diverse /{beta} TCRs with innate-like properties. These TCRs (i) have high generation probabilities and a preferential usage of some V and J genes, (ii) are shared between individuals, (iii) are highly enriched for viral antigen recognition and (iv) have a fuzzy rather than tight specificity. In vitro, T cells expressing these TCRs bind to and are activated by multiple unrelated viral peptides; in vivo, they respond to vaccination and infection, being notably found in bronchoalveolar lavages of COVID-19 infected patients. Our results support an evolutionary selection of pleiospecific /{beta}TCRs for broad antiviral responses and heterologous immunity.

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