Immunogenic T cell epitopes of SARS-CoV-2 are recognized by circulating memory and naïve CD8 T cells of unexposed individuals.
EBioMedicine
; 72: 103610, 2021 Oct.
Article
in English
| MEDLINE | ID: covidwho-1514150
ABSTRACT
BACKGROUND:
Recent studies have provided evidence of T cell reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in significant numbers of non-infected individuals, which has been attributed to cross-reactive CD4 memory T cells from previous exposure to seasonal coronaviruses. Less evidence of cross-reactive memory CD8 T cells has been documented to date.METHODS:
We used the NetCTLPan neural network of the Epitope Database and Analysis Resource to select a series of 27 HLA-A*0201 epitopes derived from the proteome of SARS-CoV-2. Their binding capacity was assessed by a HLA-A*0201 stabilization assay and by quantifying their binding to HLA-A*0201 monomers for the generation of tetramers. Their ability to stimulate and induce expansion of SARS-CoV-2 reactive CD8 T cells was measured by flow cytometry. The TCR repertoire of COVID convalescent and healthy unexposed donors was analysed using the MIRA database.FINDINGS:
The HLA-A*0201 epitopes tested were able to stabilise HLA molecules and induce activation of CD8 T cells of healthy unexposed donors. Our results, based on specific tetramer binding, provide evidence supporting the presence of frequent cross-reactive CD8 T cells to SARS-CoV-2 antigens in non-exposed individuals. Interestingly, the reactive cells were distributed into naïve, memory and effector subsets.INTERPRETATION:
Our data are consistent with a significant proportion of the reactive CD8 T clones belonging to the public shared repertoire, readily available in absence of previous contact with closely related coronaviruses. Furthermore, we demonstrate the immunogenic capacity of long peptides carrying T cell epitopes, which can serve to isolate virus-specific T cell receptors among the ample repertoire of healthy unexposed subjects and could have application in COVID-19 immunotherapy. Limitations of our study are that it concentrated on one MHC I allele (HLA-A*0201) and the low numbers of samples and epitopes tested.FUNDING:
See the Acknowledgements section.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
CD8-Positive T-Lymphocytes
/
Epitopes, T-Lymphocyte
/
SARS-CoV-2
/
COVID-19
Type of study:
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
EBioMedicine
Year:
2021
Document Type:
Article
Affiliation country:
J.ebiom.2021.103610
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