Mapping of the SARS-CoV-2 epitope-specific T-cell response using dCODE Dextramer®

Background

In this study, the CD8+ T-cell response in COVID-19 patients experiencing mild or severe disease was investigated using dCODE Dextramer® reagents by bulk and single-cell analysis.

dCODE Dextramer®

Study Description

Patient-derived T cells were initially screened for SARS-CoV-2-specificity using a panel of 38 different dCODE Dextramer® (HiT) reagents, including 4 positive and 4 negative controls. From the initial screening, a panel of 15 dCODE Dextramer® (10x) reagents plus the 8 controls were selected for subsequent single-cell analysis.

 

Results

Screening of patient samples using dCODE Dextramer® (HiT) enabled identification of samples holding specifically enriched epitope-binding T-cell populations for subsequent single-cell analysis with dCODE Dextramer® (10x), (Table 1). By clustering epitope specificity based on dCODE Dextramer® (10x) binding, researchers found unique recognition of four epitopes by T cells (Fig. 1) with the A*0101 epitope WTAGAAAYY being the most prevalent. In patients with severe COVID-19, single-cell analysis of T cells binding dCODE Dextramer® (10x) reagents revealed hyperactivation, T-cell exhaustion, and lack of long-lived memory T-cell features (Fig. 2).

Fig. 1 The four uniquely recognized epitopes identified using dCODE Dextramer® (10x) reagents are recognized by different T-cell subsets.

 

Fig. 2 Distribution of cell type frequency for active, mild, and severe COVID-19. SLEC = short-lived effector cells. MPEC = memory precursor effector cell.

 

HLA

Peptide

Target

A*0101

WTAGAAAYY

S Protein

A*0101

LTDEMIAQY

S Protein

A*0201

TLACFVLAAV

M Protein

A*0201

GMSRIGMEV

N Protein

A*0201

TLACFVLAAV

M Protein

A*0201

LLLDRLNQL

N Protein

A*0201

NLNESLIDL

S Protein

A*0201

ILLNKHIDA

N Protein

A*0201

FIAGLIAIV

M Protein

A*0301

TLKSFTVEK

S Protein

A*0301

QIYKTPPIK

S Protein

A*1101

LSYFIASFR

M Protein

A*1101

MTSCCSCLK

S Protein

A*1101

GYVFASTEK

S Protein

A*1101

TLKSFTVEK

S Protein

Table 1 Top 15 immunogenic epitopes selected in the dCODE Dextramer® (HiT) screening for single-cell immuno-profiling of patient-specific CD8+ T cells.

Conclusions

  • Relevant SARS-CoV-2 epitopes were identified in the initial screening using a panel of dCODE Dextramer® (HiT)
  • Single-cell analysis of T cells binding dCODE Dextramer® (10x) reagents identified the CD8+ T-cell epitope WTAGAAAYY
  • In patients with severe COVID-19, single-cell analysis with dCODE Dextramer® (10x) reagents revealed hyperactivation, T-cell exhaustion, and lack of long-lived memory T-cell characteristics

Download

Get the case study as a PDF.

Discover dCODE Dextramer®

Visit the dCODE Dextramer® page.

Questions?

Get in touch with our application specialists.