Immunogenic T cell epitopes of SARS-CoV-2 are recognized by circulating memory and naïve CD8 T cells of unexposed individuals

• Published in: EBioMedicine Vol. 72; p. 103610
• Main Authors: Quiros-Fernandez, Isaac, Poorebrahim, Mansour, Fakhr, Elham, Cid-Arregui, Angel
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2021; Elsevier
• Subjects: Advanced Basic Science; CD8 memory T cells; COVID-19; immunotherapy; Internal Medicine; pre-existing cross-reactivity; Research Paper; SARS-CoV-2; T cell epitopes; vaccine; COVID-19; SARS-CoV-2; vaccine; T cell epitopes; CD8 memory T cells; immunotherapy; pre-existing cross-reactivity
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2021.103610

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. We used the NetCTLPan neural network of the Epitope Database and Analysis Resource to select a series of 27 HLA-A*02:01 epitopes derived from the proteome of SARS-CoV-2. Their binding capacity was assessed by a HLA-A*02:01 stabilization assay and by quantifying their binding to HLA-A*02:01 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. The HLA-A*02:01 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. 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*02:01) and the low numbers of samples and epitopes tested. See the Acknowledgements section.