TY - JOUR T1 - Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals JF - bioRxiv DO - 10.1101/2020.05.26.115832 SP - 2020.05.26.115832 AU - Nina Le Bert AU - Anthony T Tan AU - Kamini Kunasegaran AU - Christine Y L Tham AU - Morteza Hafezi AU - Adeline Chia AU - Melissa Chng AU - Meiyin Lin AU - Nicole Tan AU - Martin Linster AU - Wan Ni Chia AU - Mark I-Cheng Chen AU - Lin-Fa Wang AU - Eng Eong Ooi AU - Shirin Kalimuddin AU - Paul Anantharajal Tambyah AU - Jenny Guek-Hong Low AU - Yee-Joo Tan AU - Antonio Bertoletti Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/27/2020.05.26.115832.abstract N2 - Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved among animal betacoranaviruses.Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.Competing Interest StatementA.B. is a cofounder of Lion TCR, a biotech company developing T cell receptors for treatment of virus-related diseases and cancers. None of the other authors has any competing interest related to the study. ER -