SARS‐CoV‐2‐reactive T‐cell receptors isolated from convalescent COVID‐19 patients confer potent T‐cell effector function
Brunk, F. et al. (2021) SARS‐CoV‐2‐reactive T‐cell receptors isolated from convalescent COVID‐19 patients confer potent T‐cell effector function Eur. J. Immunol. 51, 2651–64. DOI: 10.1002/eji.202149290
T-cell receptors (TCRs) recognize short peptide antigens on major histocompatibility complex proteins. Through signal transduction, they activate T cells, a type of white blood cell. The activated T cells trigger cytokine secretion, which lead to abnormal cells being killed, and are an important aspect of adaptive immunity. Along with B cells, these T cells are also recognized as an important part of effective anti-SARS-CoV-2 immunity. Previous studies on other types of coronaviruses showed evidence that T cell responses are important for conferring protection through memory T cells and early viral clearance. These earlier studies also demonstrated that impaired T cell activity may be associated with more severe SARS-CoV-2 disease progression.
In recent years, there has been progress in identifying and characterizing SARS-CoV-2-derived T cell epitopes and differentiating between SARS-CoV-2-specific epitopes and those that are cross-reactive with other coronaviruses. Even so, there is still limited knowledge about which TCRs drive the immune response. Factors that contribute to impaired immune function still need to be identified, as well as which TCRs are involved in responding to SARS-CoV-2.
In this study, researchers collected blood samples from convalescent COVID-19 patients and used FACS-sorting to isolate SARS-CoV-2 positive epitopes. These sorted cells were then subjected to TCR sequence retrieval through single-cell next-generation sequencing. Researchers performed reporter assays and in vitro cytotoxicity assays to characterize the SARS-CoV-2-positive TCRs. The functional assays revealed that TCRs conferred strong immune responses and are indeed capable of activating T cells to initiate an effective immune response against SARS-CoV-2. Though frequencies of CD8+ T cells recognizing SARS-CoV-2-specific epitopes in peripheral blood mononuclear cells (PBMCs) from convalescent donors were very low, they were significantly enriched compared to prepandemic control samples. These results are supported by previous studies that claim in comparison to other viral infections, tetramer-detectable SARS-CoV-2-specific CD8+ T cells are lower in COVID-19 patients. They explain that low starting frequencies of target-specific CD8+ T cells even during the acute phase as seen here, could contribute to worsened disease progression in some COVID-19 patients. Overall, the results of this study demonstrate how TCRs isolated from convalescent COVID-19 patients conferred potent T cell effector function by increasing cytokine production and target cell killing. Findings from this study expand on current understandings of SARS-CoV-2 T cell immunity and could be beneficial for developing immunotherapies.
Keywords: COVID‐19, SARS‐CoV‐2, single‐cell sequencing, T‐cell receptor, viral immunity
