tetano
Editor, Senior Moderator
Science
. 2020 Aug 4;eabd3871.
doi: 10.1126/science.abd3871. Online ahead of print.
Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
Jose Mateus[SUP] 1 [/SUP], Alba Grifoni[SUP] 1 [/SUP], Alison Tarke[SUP] 1 [/SUP], John Sidney[SUP] 1 [/SUP], Sydney I Ramirez[SUP] 1 2 [/SUP], Jennifer M Dan[SUP] 1 2 [/SUP], Zoe C Burger[SUP] 2 [/SUP], Stephen A Rawlings[SUP] 2 [/SUP], Davey M Smith[SUP] 2 [/SUP], Elizabeth Phillips[SUP] 3 [/SUP], Simon Mallal[SUP] 3 [/SUP], Marshall Lammers[SUP] 1 [/SUP], Paul Rubiro[SUP] 1 [/SUP], Lorenzo Quiambao[SUP] 1 [/SUP], Aaron Sutherland[SUP] 1 [/SUP], Esther Dawen Yu[SUP] 1 [/SUP], Ricardo da Silva Antunes[SUP] 1 [/SUP], Jason Greenbaum[SUP] 1 [/SUP], April Frazier[SUP] 1 [/SUP], Alena J Markmann[SUP] 4 [/SUP], Lakshmanane Premkumar[SUP] 5 [/SUP], Aravinda de Silva[SUP] 5 [/SUP], Bjoern Peters[SUP] 1 2 [/SUP], Shane Crotty[SUP] 1 2 [/SUP], Alessandro Sette[SUP] #[/SUP][SUP] 6 2 [/SUP], Daniela Weiskopf[SUP] #[/SUP][SUP] 6 [/SUP]
Affiliations
Abstract
Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cell repertoire. We demonstrate a range of pre-existing memory CD4[SUP]+[/SUP] 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.
. 2020 Aug 4;eabd3871.
doi: 10.1126/science.abd3871. Online ahead of print.
Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
Jose Mateus[SUP] 1 [/SUP], Alba Grifoni[SUP] 1 [/SUP], Alison Tarke[SUP] 1 [/SUP], John Sidney[SUP] 1 [/SUP], Sydney I Ramirez[SUP] 1 2 [/SUP], Jennifer M Dan[SUP] 1 2 [/SUP], Zoe C Burger[SUP] 2 [/SUP], Stephen A Rawlings[SUP] 2 [/SUP], Davey M Smith[SUP] 2 [/SUP], Elizabeth Phillips[SUP] 3 [/SUP], Simon Mallal[SUP] 3 [/SUP], Marshall Lammers[SUP] 1 [/SUP], Paul Rubiro[SUP] 1 [/SUP], Lorenzo Quiambao[SUP] 1 [/SUP], Aaron Sutherland[SUP] 1 [/SUP], Esther Dawen Yu[SUP] 1 [/SUP], Ricardo da Silva Antunes[SUP] 1 [/SUP], Jason Greenbaum[SUP] 1 [/SUP], April Frazier[SUP] 1 [/SUP], Alena J Markmann[SUP] 4 [/SUP], Lakshmanane Premkumar[SUP] 5 [/SUP], Aravinda de Silva[SUP] 5 [/SUP], Bjoern Peters[SUP] 1 2 [/SUP], Shane Crotty[SUP] 1 2 [/SUP], Alessandro Sette[SUP] #[/SUP][SUP] 6 2 [/SUP], Daniela Weiskopf[SUP] #[/SUP][SUP] 6 [/SUP]
Affiliations
- PMID: 32753554
- DOI: 10.1126/science.abd3871
Abstract
Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cell repertoire. We demonstrate a range of pre-existing memory CD4[SUP]+[/SUP] 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.