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.
Keywords: COVID-19; SARS-CoV-2; T-cell receptor; single-cell sequencing.
【저자키워드】 COVID-19, SARS-CoV-2, T-cell receptor, single-cell sequencing, 【초록키워드】 immune response, Immunity, Neutralizing antibodies, T cells, Sequencing, B cells, cytotoxicity, in vitro, virus, CD4, CD8, anti-SARS-CoV-2, Population, B cell, T cell, Characteristics, T-cell receptor, T-cell, convalescent, reporter, TCR, single-cell, IFN-γ, T-cell immunity, convalescent COVID-19 patients, HLA-A*02:01, memory response, Signaling, HLA-A, EC50 values, help, clone, while, TCRs, approach, effective, robust, initial, described, example, involved, detectable, generate, functional, contribute, long-lasting, disease-causing, ectopic, retrieved, 【제목키워드】 T-cell, convalescent COVID-19 patient,