Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients
cell biology clinical immunology/immunity inflammation
Authors:Peng, Y., Mentzer, A. J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W. et al.
Link to paper: https://doi.org/10.1101/2020.06.05.134551
Tags: Cell Biology, Clinical, Immunology/Immunity, Inflammation
1. Breadth and magnitude of SARS-Cov-2 memory T cells were significantly higher in patients recovered from severe disease in comparison to mild cases. M/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.
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
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.