SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

Authors: Shomuradova et al.

Link to paper: https://doi.org/10.1101/2020.05.20.20107813

Journal/ Pre-Print: medRxiv

Key Words: Immunology

Research Highlights

1. SARS-CoV-2-specific T cells are increased in healthy donors examined during COVID-19 suggesting that some individuals might be protected by T-cell cross-reactivity

2. In convalescent patients both a public and diverse T-cell response to SARS-CoV-2 epitopes were observed, revealing T-cell receptor motifs with germline-encoded features

3. Bulk T-cell responses to Spike (S) glycoprotein were mediated by groups of homologous T-cell receptors, of which some are shared between multiple donors

Summary 

Antibody and T-cell reactivity was analysed in 31 COVID-19 convalescent patients (CP), compared to healthy donors (HD) sampled prior to (20) or during (14) the pandemic. All bar two CPs had IgG specific to SARS-CoV-2 antigens. T-cell responses to S-protein were highly variable with some CPs lacking response. All CPs exhibited T-cell reactivity to at least one SARS CoV-2 protein. CPs can be discriminated from HDs by response to two HLA-A*02:01-restricted SARS-CoV-2 S-protein epitopes. High-throughput TCR sequencing of FACS-sorted IFNg-secreting T cells showed that TCRs specific to the two SARS-CoV-2 epitopes are characterized by diverse public motifs.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Study Type

· In vitro study

Strengths and limitations of the paper

Novelty: Confirms some previous findings in terms of T-cell reactivity against SARS-CoV-2 but profiles the TCR repertoire more thoroughly

Standing in the field: Many of their findings appear to be consistent with previous reports while some do not support previous findings (e.g. no correlation between anti-SARS-CoV-2 antibody titres and patient age)

Appropriate statistics: Yes. For Figure 2a and 2b it would have been useful to be able to see the variation

Viral model used: PBMCs of COVID-19-confirmed patients and healthy donors

Translatability: The finding that the immune response to two HLA-A*02:01-restricted SARS-CoV-2 S-protein epitopes distinguishes convalescent from healthy donors could potentially be useful for vaccine development. The presence of SARS-CoV-2 specific IgG antibodies in convalescent patients and their complete absence in healthy donors confirms the utility of this assay to identify individuals previously exposed to the virus.

Main limitations: The authors use IFNg-secretion upon stimulation as a readout of antigen-specific cells, which might miss some relevant T cells. Also, none of the CPs had severe disease (requiring ICU admission)