Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

 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 # 6 2, Daniela Weiskopf # 6

• DOI: 10.1126/science.abd3871

PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32753554/

Abstract

Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2-reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 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 preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, and 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 coronavirus disease 2019 (COVID-19) disease.

https://pubmed.ncbi.nlm.nih.gov/32753554/