Abstract
A better understanding of the role of T cells in the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is helpful not only for vaccine development but also for the treatment of COVID-19 patients. In this study, we determined the existence of SARS-CoV-2-specific T cells in the blood of COVID-19 convalescents. Meanwhile, the specific T cell response in the non-RBD region was stronger than in the RBD region. We also found that SARS-CoV-2 S-specific reactive CD4+ T cells exhibited higher frequency than CD8+ T cells in recovered COVID-19 patients, with greater number of corresponding epitopes presented. Importantly, we isolated the SARS-CoV-2-specific CD4+ T cell receptors (TCRs) and inserted the TCRs into allogenic CD4+ T cells. These TCR-T cells can be activated by SARS-CoV-2 spike peptide and produce IFN-γ in vitro. These results might provide valuable information for the development of vaccines and new therapies against COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the cause of coronavirus disease 2019 (COVID-19)
We found that T cells responding to multiple regions of the S protein do exist in the peripheral blood mononuclear cells (PBMCs) of all recovered COVID-19 patients
These results indicated that the PBMCs of recovered COVID-19 patients contained specific populations of T cells with high reactivity to SARS-CoV-2 S protein, of which the RBD region might induce a relatively lower level of T cell responses
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the cause of coronavirus disease 2019 (COVID-19). T Cell Immunity of SARS-CoV-2 reported to decrease both in most of the asymptomatic and symptomatic groups during the early convalescent phase (Long et al, 2020), with no high concentration of neutralizing activity found even in most recovered plasma samples (Li et al, 2020; Robbiani et al, 2020), suggesting that the effective window for the neutralizing antibody induced by vaccines may be relatively limited. According to the research of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), T cell immunity plays a decisive part in the disease recovery and long-lasting protection (Zhao et al, 2010, 2016; Channappanavar et al, 2014a; Ng et al, 2016). It is crucial to obtain SARS-CoV-2-specific TCRs with high functionalities for the immunological protection of this highly mutated coronavirus
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