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*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. Findings 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. 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*02:01) and the low numbers of samples and epitopes tested.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, Immunotherapy, T cell epitopes, pre-existing cross-reactivity, CD8 memory T cells, 【초록키워드】 Coronaviruses, peptide, CD4, CD8, database, coronavirus 2, flow cytometry, memory, COVID, T cell, proteome, receptor, donors, SARS-CoV-2 antigen, seasonal coronaviruses, respiratory, convalescent, epitope, TCR, memory T cell, Donor, binding, HLA-A*02:01, Evidence, Contact, CD8 T cell, cross-reactive, Activation, subject, naïve, immunogenic, limitation, allele, finding, monomer, clone, MHC I, recent, Cell, reactive, non-infected, was measured, tested, proportion, healthy, provided, analysed, absence, induce, individuals, reactivity, stimulate, virus-specific T cell, HLA molecule, 【제목키워드】 memory, T cell epitope, CD8 T cell, individual, naïve, circulating,