SARS‐CoV‐2‐specific CD8⁺ T‐cell responses and TCR signatures in the context of a prominent HLA‐A*24:02 allomorph

Jun 4, 2021Immunology and cell biology

SARS-CoV-2-specific killer T-cell responses and receptor patterns linked to the common HLA-A*24:02 type

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Abstract

Three specific SARS-CoV-2 peptides showed significant immune response in COVID-19 patients.

Three spike-derived peptides, S(QYIKWPWYI), S(NYNYLYRLF), and S(VFKNIDGYF), generated stronger immune responses than background levels.
The peptide S elicited the strongest immune response among those tested.
Precursor frequencies for -restricted epitopes were similar to other known SARS-CoV-2 epitopes.
Naïve A24/SARS-CoV-2-specific CD8 T cells increased nearly 7.5-fold in frequency during COVID-19.
The TCRαβ repertoire of A24/SCD8 T cells was diverse among patients, driven by a common TCRβ chain motif.
These findings may enhance understanding of immune responses in COVID-19 and inform vaccine strategies.

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In-depth understanding of human T-cell-mediated immunity in coronavirus disease 2019 (COVID-19) is needed if we are to optimize vaccine strategies and immunotherapies. Identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell epitopes and generation of peptide-human leukocyte antigen (peptide-HLA) tetramers facilitate direct ex vivo analyses of SARS-CoV-2-specific T cells and their T-cell receptor (TCR) repertoires. We utilized a combination of peptide prediction and in vitro peptide stimulation to validate novel SARS-CoV-2 epitopes restricted by HLA-A24:02, one of the most prominent HLA class I alleles, especially in Indigenous and Asian populations. Of the peptides screened, three spike-derived peptides generated CD8IFNγresponses above background, S(QYIKWPWYI), S(NYNYLYRLF) and S(VFKNIDGYF), with Sgenerating immunodominant CD8IFNγresponses. Using peptide-HLA-I tetramers, we performed direct ex vivo tetramer enrichment for HLA-A24:02-restricted CD8T cells in COVID-19 patients and prepandemic controls. The precursor frequencies for HLA-A24:02-restricted epitopes were within the range previously observed for other SARS-CoV-2 epitopes for both COVID-19 patients and prepandemic individuals. Naïve A24/SARS-CoV-2-specific CD8T cells increased nearly 7.5-fold above the average precursor frequency during COVID-19, gaining effector and memory phenotypes. Ex vivo single-cell analyses of TCRαβ repertoires found that the A24/SCD8T-cell TCRαβ repertoire was driven by a common TCRβ chain motif, whereas the A24/SCD8TCRαβ repertoire was diverse across COVID-19 patients. Our study provides an in depth characterization and important insights into SARS-CoV-2-specific CD8T-cell responses associated with a prominent HLA-A24:02 allomorph. This contributes to our knowledge on adaptive immune responses during primary COVID-19 and could be exploited in vaccine or immunotherapeutic approaches. + + + + + + + + + + + 1208-1216 448-456 193-201 1208 448 1208

Key numbers

7.5×

Increase in Naïve A24/SARS-CoV-2-specific

Naïve increased nearly 7.5× during COVID-19.

6.3 × 10

of A24/SCD8+ T cells

Mean of A24/SCD8+ T cells in COVID-19 convalescent donors.

8.44 × 10

of A24/SCD8+ T cells in prepandemic individuals

Mean of A24/SCD8+ T cells in prepandemic healthy individuals.

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Abstract

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