Jose Mateus 1 , Alba Grifoni 1 , Alison Tarke 1 , John Sidney 1 , Sydney I. Ramirez 1 , 2 , Jennifer M. Dan 1 , 2 , Zoe C. Burger 2 , Stephen A. Rawlings 2 , Davey M. Smith 2 , Elizabeth Phillips 3 , Simon Mallal 3 , Marshall Lammers 1 , Paul Rubiro 1 , Lorenzo Quiambao 1 , Aaron Sutherland 1 , Esther Dawen Yu 1 , Ricardo da Silva Antunes 1 , Jason Greenbaum 1 , April Frazier 1 , Alena J. Markmann 4 , Lakshmanane Premkumar 5 , Aravinda de Silva 5 , Bjoern Peters 1 , 2 , Shane Crotty 1 , 2 , Alessandro Sette 1 , 2 , Daniela Weiskopf 1
August 04 2020
Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4 + T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4 + T cell repertoire. We demonstrate a range of pre-existing memory CD4 + T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.