SARS-CoV-2-Seronegative Subjects Target CTL Epitopes in the SARS-CoV-2 Nucleoprotein Cross-Reactive to Common Cold Coronaviruses

• Published in: Frontiers in immunology Vol. 12; p. 627568
• Main Authors: Schmidt, Katja G., Nganou-Makamdop, Krystelle, Tenbusch, Matthias, El Kenz, Boutaina, Maier, Clara, Lapuente, Dennis, Überla, Klaus, Spriewald, Bernd, Bergmann, Silke, Harrer, Ellen G., Harrer, Thomas
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.04.2021
• Subjects: Adult; Aged; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8+ T-cell; Cell Line; Common Cold - genetics; Common Cold - immunology; Common Cold - pathology; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - pathology; Cross Reactions; CTL; CTL epitope; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; HKU1; Humans; Immunology; Male; Middle Aged; Nucleoproteins - genetics; Nucleoproteins - immunology; OC43; SARS-CoV-2 (2019-nCoV); SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; HIV-1; SARS-CoV-2 (2019-nCoV); CTL epitope; OC43; CD8+ T-cell; CTL; HKU1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.627568

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.