التفاصيل البيبلوغرافية
| العنوان: |
Human thymopoiesis produces polyspecific CD8+ α/β T cells responding to multiple viral antigens. |
| المؤلفون: |
Quiniou, Valentin1,2, Barennes, Pierre1,2, Mhanna, Vanessa1,2, Stys, Paul1, Vantomme, Helene1,2, Zhicheng Zhou2, Martina, Federica2, Coatnoan, Nicolas2, Barbie, Michele2, Hang-Phuong Pham3, Clémenceau, Béatrice4, Vie, Henri4, Shugay, Mikhail5, Six, Adrien1, Brandao, Barbara3, Mallone, Roberto3,6, Mariotti-Ferrandiz, Encarnita1, Klatzmann, David1,2 david.klatzmann@sorbonneuniversite.fr |
| المصدر: |
eLife. 3/30/2023, p1-24. 24p. |
| مصطلحات موضوعية: |
*VIRAL antigens, *T cells, *GENE rearrangement, *T cell receptors, *IMMUNE response, *CD8 antigen |
| مستخلص: |
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 can effectively handle a countless and evolving set of 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 effective immune response and enough antigen-experienced cells for memory. We show here that human thymopoiesis releases a large population of clustered CD8+ T cells harboring α/β paired TCRs that (i) have high generation probabilities and (ii) a preferential usage of some V and J genes, (iii) which CDR3 are shared between individuals, and (iv) can each bind and be activated by multiple unrelated viral peptides, notably from EBV, CMV, and influenza. These polyspecific T cells may represent a first line of defense that is mobilized in response to infections before a more specific response subsequently ensures viral elimination. Our results support an evolutionary selection of polyspecific α/β TCRs for broad antiviral responses and heterologous immunity. [ABSTRACT FROM AUTHOR] |
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