SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition

SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition
Nelde A., Bilich T., Heitmann JS., Maringer Y., Salih HR., Roerden R., Luebke M., Bauer J., Rieth J., Wacker M., Peter A., Hörber S., Traenkle B., Kaiser PD., Rothbauer U., Becker M., Junker D., Krause G., Strengert M., Schneiderhan-Marra N., Joos TO., Kowalewski D.J., Stos-Zweifel V., Fehr M., Graf M., Gruber L., Rachfalski D., Preuß B., Hagelstein I., Märklin M., Bakchoul T., Gouttefangeas C., Kohlbacher O., Klein R., Stevanović S., Rammensee H.-G., Walz J.S.
Nature Immunology 2021; 22:74–85, DOI: 10.1038/s41590-020-00808-x

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.