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

Shomuradova, Alina S.; Vagida, Murad S.; Sheetikov, Savely A.; Zornikova, Ksenia V.; Kiryukhin, Dmitry; Titov, Aleksei; Peshkova, Iuliia O.; Khmelevskaya, Alexandra; Dianov, Dmitry V.; Malasheva, Maria; Shmelev, Anton; Serdyuk, Yana; Bagaev, Dmitry V.; Pivnyuk, Anastasia; Shcherbinin, Dmitrii S.; Maleeva, Alexandra V.; Shakirova, Naina T.; Pilunov, Artem; Malko, Dmitry B.; Khamaganova, Ekaterina G.; Biderman, Bella; Ivanov, Alexander; Shugay, Mikhail; Efimov, Grigory A.

Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion, or activation of pre-existing immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4+ and CD8+ T cell responses to the spike glycoprotein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.