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Authors:Peng, Y., Mentzer, A. J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W. et al. 

Journal/ Pre-Print:bioRxiv 

Tags: Cell Biology, Clinical, Immunology/Immunity, Inflammation 

Research Highlights

1. Breadth and magnitude of SARS-Cov-2 memory T cells were significantly higher in patients recovered from severe disease in comparison to mild casesM/NP-specific CD8+ T cells were observed in higher frequencies than spike-specific CD8+ T cells in those with mild disease, and were more poly-functional  

2. Specific SARS-Cov-2 T cells were not frequently observed in healthy, unexposed individuals (in contrast to a previous report by Grifoni et al. (2020) Cell). Furthermore, the magnitude of T cell responses in Covid-19 patients correlated with their antibody titres (anti-spike, anti-RBD and anti-NP). 

3. Six immunodominant epitope clusters were identified (based on IFNγ production by T cells), and showed low similarity to epitopes from other coronaviruses. 

Summary

The present study characterizes the magnitude and functionality of SARS-CoV-2 specific memory T cells (both CD4+ and CD8+) from recovered Covid-19 patients taking into account previous disease severity. Using overlapping peptides spanning SARS-CoV-2 (except ORF1) and IFN-g production as a readout for specific T cell responses, authors were able to show that the breadth and magnitude of memory T cells were significantly higher in severe disease compared with mild cases. However, membrane (M)/nucleoprotein (NP)-specific CD8+ T cells were observed in higher frequencies than spike-specific CD8+ T cells in those who recovered from mild disease, and these cells also showed to be more poly-functional (based on cytokine production). Corroborating previous reports, both total and spike-specific T cell responses positively correlated with anti-spike, anti-receptor-binding-domain (RBD), and anti-NP antibody titres. Strikingly, they found six immunodominant peptide clusters (including 3 spike, 2 M, 1 NP). Further investigation of HLA-restriction-defined CD8+ responses identified B*4001-restricted T cells showing both central memory and effector memory phenotype. The epitope clusters/peptides containing T cell epitopes identified by this study can play an important role in the development of vaccines targeting T cell responses, and suggest the potential importance of poly-functional non-spike-specific CD8+ T cells in SARS-CoV-2 efficient immune responses.   

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19, especially the T cell response 

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19 

Study Type  

  • In vitro study 

  • Patient Case study 

Strengths and limitations of the paper 

Novelty: Characterization of immunodominant T cell epitopes and T cell immunity in recovered Covid-19 patients considering the disease severity 

Standing in the field:Recent publications have investigated epitope/peptide targets of T cell responses and characterized CD4/CD8 memory T cell immunity against SARS-CoV-2, but the present study is very well performed and further stratifies the analysis based on disease severity 

Appropriate statistics: The statistical tools used are very clear and all listed in the method section of the paper  

Viral model used:Original SARS-CoV2 from patients, confirmed by RT-PCR 

Translatability:These findings could play a crucial role in understanding T cell responses in mild/severe disease progression and the immunodominant peptides they found could be used for vaccine design. 

Main limitations: Further investigation in a larger cohort is necessary to elucidate whether the responses to immunodominant epitopes play a protective role against SARS-CoV-2.