SARS-CoV-2-reactive T-cell receptors isolated from convalescent COVID-19 patients confer potent T-cell effector function |
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Authors: | Fabian Brunk Andreas Moritz Annika Nelde Tatjana Bilich Nicolas Casadei Sabine A. K. Fraschka Jonas S. Heitmann Sebastian Hörber Andreas Peter Hans-Georg Rammensee Harpreet Singh Juliane Walz Dominik Maurer Claudia Wagner |
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Affiliation: | 1. Immatics N.V., Tübingen, Germany;2. Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany;3. NGS Competence Center Tübingen, Tübingen, Germany;4. Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, Tübingen, Germany;5. Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany |
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Abstract: | Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells—with the indispensable help of CD4+ T cells—are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8+ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2. |
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Keywords: | COVID-19 SARS-CoV-2 single-cell sequencing T-cell receptor |
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