SARS‐CoV‐2‐reactive T‐cell receptors isolated from convalescent COVID‐19 patients confer potent T‐cell effector function

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*24:02restricted 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

Delineating COVID-19 immunological features using single-cell RNA sequencing

“…Although there are many studies using infected animals for COVID-19 research, 87,88 only a few studies performed scRNA-seq on COVID-19-infected animals like monkeys, 89 hamsters, 90 macaques, 91 ferrets, 92 and K18-hACE2 transgenic mice. 93 Several studies demonstrated the antiviral immune responses of animal models after receiving newly developed vaccines with scRNA-seq, [94][95][96][97] revealing induced gene modules of different immune cell populations. As it is much easier to obtain samples from various organs in animal models than in human patients and at consecutive time points after COVID-19 infection, vaccination, or therapy, performing temporalspatial analysis at the single-cell resolution in animal models for COVID-19 could be a promising future direction.…”

Progress and Challenges Toward Generation and Maintenance of Long-Lived Memory T Lymphocyte Responses During COVID-19

“…Antigen-primed T cells are crucial to effectively countering the SARS-CoV-2 infection mediated by both CD4 + and CD8 + Teff cells ( 66 ). T cell response investigated against nucleocapsid (N) protein has been shown to exhibit robust IFN-γ response after 17 years of SARS-CoV infection against N peptides.…”

AIDS patient with severe T cell depletion achieved control but not clearance of SARS‐CoV‐2 infection

“…So far, T cells are considered to have a dominant role in the control and clearance of SARS‐CoV‐2 infection [ 14 , 15 ]. Several cases of fully recovered SARS‐CoV‐2 infection in patients with genetic or pharmacological B cell depletion for the unrelated condition have been reported, suggesting that a protective immune response against SARS‐CoV‐2 can be produced even without humoral immunity [ 16 , 17 ].…”