The beta-coronavirus SARS-CoV-2 induces severe disease (COVID-19) mainly in elderly persons with risk factors, whereas the majority of patients experience a mild course of infection. As the circulating common cold coronaviruses OC43 and HKU1 share some homologous sequences with SARS-CoV-2, beta-coronavirus cross-reactive T-cell responses could influence the susceptibility to SARS-CoV-2 infection and the course of COVID-19. To investigate the role of beta-coronavirus cross-reactive T-cells, we analyzed the T-cell response against a 15 amino acid long peptide (SCoV-DP15: DLSPRWYFYYLGTGP) from the SARS-CoV-2 nucleoprotein sequence with a high homology to the corresponding sequence (QLLPRWYFYYLGTGP) in OC43 and HKU1. SCoV-DP15-specific T-cells were detected in 4 out of 23 (17.4%) SARS-CoV-2-seronegative healthy donors. As HIV-1 infection is a potential risk factor for COVID-19, we also studied a cohort of HIV-1-infected patients on antiretroviral therapy. 44 out of these 116 HIV-1-infected patients (37.9%) showed a specific recognition of the SCoV-DP15 peptide or of shorter peptides within SCoV-DP15 by CD4 + T-cells and/or by CD8 + T-cells. We could define several new cross-reactive HLA-I-restricted epitopes in the SARS-CoV-2 nucleoprotein such as SPRWYFYYL (HLA-B*07, HLA-B*35), DLSPRWYFYY (HLA-A*02), LSPRWYFYY (HLA-A*29), WYFYYLGTGP and WYFYYLGT. Epitope specific CD8 + T-cell lines recognized corresponding epitopes within OC43 and HKU1 to a similar degree or even at lower peptide concentrations suggesting that they were induced by infection with OC43 or HKU1. Our results confirm that SARS-CoV-2-seronegative subjects can target SARS-CoV-2 not only by beta-coronavirus cross-reactive CD4 + T-cells but also by cross-reactive CD8 + cytotoxic T-cells (CTL). The delineation of cross-reactive T-cell epitopes contributes to an efficient epitope-specific immunomonitoring of SARS-CoV-2-specific T-cells. Further prospective studies are needed to prove a protective role of cross-reactive T-cells and their restricting HLA alleles for control of SARS-CoV-2 infection. The frequent observation of SARS-CoV-2-reactive T-cells in HIV-1-infected subjects could be a reason that treated HIV-1 infection does not seem to be a strong risk factor for the development of severe COVID-19.
【저자키워드】 SARS-CoV-2 (2019-nCoV), HIV-1, CTL epitope, CD8+ T-cell, CTL, OC43, HKU1, 【초록키워드】 COVID-19, SARS-CoV-2, Risk factors, severe COVID-19, SARS-COV-2 infection, susceptibility, T-cell Response, Prospective Study, T-cells, Infection, peptide, risk factor, CD4, CD8, Epitopes, Cohort, Antiretroviral therapy, HIV-1, Patient, peptides, Mild, Beta, common cold, T-cell, homologous, epitope, T-cell epitope, OC43, HKU1, T-cell responses, Amino acid, HLA-B, Concentration, severe disease, beta-coronavirus, cross-reactive, observation, HLA-A, healthy donors, subject, potential risk, sequence, HLA alleles, common cold coronavirus, protective role, reason, homology, HLA allele, circulating, SARS-CoV-2 nucleoprotein, HIV-1 infection, delineation, HLA-A*02, Course, analyzed, treated, majority, contribute, induce, the SARS-CoV-2, 【제목키워드】 Epitopes, target, common cold, nucleoprotein, Cold, common, the SARS-CoV-2,