Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

• Published in: Nature immunology Vol. 21; no. 11; pp. 1336 - 1345
• Main Authors: Peng, Yanchun, Mentzer, Alexander J., Liu, Guihai, Yao, Xuan, Yin, Zixi, Dong, Danning, Dejnirattisai, Wanwisa, Rostron, Timothy, Supasa, Piyada, Liu, Chang, López-Camacho, César, Slon-Campos, Jose, Zhao, Yuguang, Stuart, David I., Paesen, Guido C., Grimes, Jonathan M., Antson, Alfred A., Bayfield, Oliver W., Hawkins, Dorothy E. D. P., Ker, De-Sheng, Wang, Beibei, Turtle, Lance, Subramaniam, Krishanthi, Thomson, Paul, Zhang, Ping, Dold, Christina, Ratcliff, Jeremy, Simmonds, Peter, de Silva, Thushan, Sopp, Paul, Wellington, Dannielle, Rajapaksa, Ushani, Chen, Yi-Ling, Salio, Mariolina, Napolitani, Giorgio, Paes, Wayne, Borrow, Persephone, Kessler, Benedikt M., Fry, Jeremy W., Schwabe, Nikolai F., Semple, Malcolm G., Baillie, J. Kenneth, Moore, Shona C., Openshaw, Peter J. M., Ansari, M. Azim, Dunachie, Susanna, Barnes, Eleanor, Frater, John, Kerr, Georgina, Goulder, Philip, Lockett, Teresa, Levin, Robert, Zhang, Yonghong, Jing, Ronghua, Ho, Ling-Pei, Cornall, Richard J., Conlon, Christopher P., Klenerman, Paul, Screaton, Gavin R., Mongkolsapaya, Juthathip, McMichael, Andrew, Knight, Julian C., Ogg, Graham, Dong, Tao
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2020; Nature Publishing Group
• Subjects: 631/250/2152/1566/1571; 692/699/255/2514; Antigens, Viral - immunology; Betacoronavirus - immunology; Biomedical and Life Sciences; Biomedicine; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - prevention & control; Coronaviruses; COVID-19; COVID-19 Vaccines; Epitopes; Epitopes, T-Lymphocyte - immunology; Humans; Immunodominant Epitopes - immunology; Immunologic Memory - immunology; Immunological memory; Immunology; Infectious Diseases; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Memory cells; Pandemics; Peptides; Phenotypes; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Proteomes; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; United Kingdom; Vaccines; Viral Vaccines - immunology; γ-Interferon; United Kingdom
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-020-0782-6

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4 + and/or CD8 + epitopes, including six immunodominant regions. Six optimized CD8 + epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8 + T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design. Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4 + and CD8 + T cells that recognize multiple epitopes that span the viral proteome. CD4 + T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8 + T cells were found in patients with mild disease.