| Autor: |
Sebastian Jarosch, Ulrike Protzer, Marcus Odendahl, Simone Weber, Andreas Pichlmair, Hedwig Roggendorf, Behnam Kalali, Karolin I. Wagner, Andrea Stroetges-Achatz, Claudia S. Crowell, Percy A. Knolle, Henriette Beyer, Verena Haselmann, Markus Gerhard, Torsten Tonn, Michael Neumaier, Johanna Erber, Holger Poppert, Kilian Schober, Teresa Burrell, K. Witter, Sarah Yazici, Stefan Holdenrieder, Sophia E. Schambeck, Dirk H. Busch, Hrvoje Mijočević, Elvira D Ippolito, Vincent Grass, Andrea Dick, Laura Mateyka, Monika Hammel, Alina Priller |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.07.20.21260845 |
| Popis: |
T cell immunity is crucial for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has been widely characterized on a quantitative level. In contrast, the quality of such T cell responses has been poorly investigated, in particular in the case of CD8+T cells. Here, we explored the quality of SARS-CoV-2-specific CD8+T cell responses in individuals who recovered from mild symptomatic infections, through which protective immunity should develop, by functional characterization of their T cell receptor (TCR) repertoire. CD8+T cell responses specific for SARS-CoV-2-derived epitopes were low in frequency but could be detected robustly early as well as late - up to twelve months - after infection. A pool of immunodominant epitopes, which accurately identified previous SARS-CoV-2 infections, was used to isolate TCRs specific for epitopes restricted by common HLA class I molecules. TCR-engineered T cells showed heterogeneous functional avidity and cytotoxicity towards virus-infected target cells. High TCR functionality correlated with gene signatures of T cell function and activation that, remarkably, could be retrieved for each epitope:HLA combination and patient analyzed. Overall, our data demonstrate that highly functional HLA class I TCRs are recruited and maintained upon mild SARS-CoV-2 infection. Such validated epitopes and TCRs could become valuable tools for the development of diagnostic tests determining the quality of SARS-CoV-2-specific CD8+T cell immunity, and thereby investigating correlates of protection, as well as to restore functional immunity through therapeutic transfer of TCR-engineered T cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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