SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

Shomuradova, A. S.; Vagida, M. S.; Sheetikov, S. A.; Zornikova, K. V.; Kiryukhin, D.; Titov, A.; Peshkova, I. O.; Khmelevskaya, A.; Dianov, D. V.; Malasheva, M.; Shmelev, A.; Serdyuk, Y.; Bagaev, D. V.; Pivnyuk, A.; Shcherbinin, D. S.; Maleeva, A. V.; Shakirova, N. T.; Pilunov, A.; Malko, D. B.; Khamaganova, E. G.; Biderman, B.; Ivanov, A. V.; Shugay, M.; Efimov, G. A.

Understanding the determinants of adaptive immune response to SARS-CoV-2 is critical for fighting the ongoing COVID-19 pandemic. Here we assayed both antibody and T-cell reactivity to SARS-CoV-2 antigens in COVID-19 convalescent patients and healthy donors sampled before and during the pandemic. Our results show that while anti-SARS-CoV-2 antibodies can distinguish convalescent patients from healthy donors, the magnitude of T-cell response was more pronounced in healthy donors sampled during COVID-19 pandemic than in donors sampled before the outbreak. This hints at the possibility that some individuals have encountered the virus but were protected by T-cell cross-reactivity observed. A public and diverse T-cell response was observed for two A*02-restricted SARS-CoV-2 epitopes, revealing a set of T-cell receptor motifs displaying germline-encoded features. Bulk CD4+ and CD8+ T-cell response to SARS-CoV-2 glycoprotein S is characterized by multiple groups of homologous T-cell receptor sequences some of which are shared across multiple donors, indicating the existence of immunodominant epitopes. Overall, our findings indicate that T cells form an efficient response to SARS-CoV-2 and alongside the antibodies can serve as a useful biomarker for surveying SARS-CoV-2 exposure and immunity. We hope that data, including the set of specific T-cell receptors identified in this study can serve as a basis for future developments of SARS-CoV-2 vaccinations and monitoring.