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

被引:807
作者
Mateus, Jose [1 ]
Grifoni, Alba [1 ]
Tarke, Alison [1 ]
Sidney, John [1 ]
Ramirez, Sydney, I [1 ,3 ]
Dan, Jennifer M. [1 ,3 ]
Burger, Zoe C. [3 ]
Rawlings, Stephen A. [3 ]
Smith, Davey M. [3 ]
Phillips, Elizabeth [2 ]
Mallal, Simon [2 ]
Lammers, Marshall [1 ]
Rubiro, Paul [1 ]
Quiambao, Lorenzo [1 ]
Sutherland, Aaron [1 ]
Yu, Esther Dawen [1 ]
Antunes, Ricardo da Silva [1 ]
Greenbaum, Jason [1 ]
Frazier, April [1 ]
Markmann, Alena J. [4 ]
Premkumar, Lakshmanane [5 ]
de Silva, Aravinda [5 ]
Peters, Bjoern [1 ,3 ]
Crotty, Shane [1 ,3 ]
Sette, Alessandro [1 ,3 ]
Weiskopf, Daniela [1 ]
机构
[1] La Jolla Inst Immunol, Ctr Infect Dis & Vaccine Res, La Jolla, CA 92037 USA
[2] Murdoch Univ, Inst Immunol & Infect Dis, Perth, WA 6150, Australia
[3] Univ Calif San Diego, Dept Med, Div Infect Dis & Global Publ Hlth, La Jolla, CA 92037 USA
[4] Univ N Carolina, Dept Med, Div Infect Dis, Sch Med, Chapel Hill, NC 27599 USA
[5] Univ N Carolina, Dept Microbiol & Immunol, Sch Med, Chapel Hill, NC 27599 USA
关键词
FOLLICULAR HELPER-CELLS; HUMAN CORONAVIRUSES; RECOGNITION;
D O I
10.1126/science.abd3871
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:89 / +
页数:47
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