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Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans.
Science. 2020 10 02; 370(6512):89-94.Sci

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.

Authors+Show Affiliations

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA 6150, Australia.Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA 6150, Australia.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. alex@lji.org daniela@lji.org. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. alex@lji.org daniela@lji.org.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32753554

Citation

Mateus, Jose, et al. "Selective and Cross-reactive SARS-CoV-2 T Cell Epitopes in Unexposed Humans." Science (New York, N.Y.), vol. 370, no. 6512, 2020, pp. 89-94.
Mateus J, Grifoni A, Tarke A, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020;370(6512):89-94.
Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S. I., Dan, J. M., Burger, Z. C., Rawlings, S. A., Smith, D. M., Phillips, E., Mallal, S., Lammers, M., Rubiro, P., Quiambao, L., Sutherland, A., Yu, E. D., da Silva Antunes, R., Greenbaum, J., Frazier, A., ... Weiskopf, D. (2020). Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science (New York, N.Y.), 370(6512), 89-94. https://doi.org/10.1126/science.abd3871
Mateus J, et al. Selective and Cross-reactive SARS-CoV-2 T Cell Epitopes in Unexposed Humans. Science. 2020 10 2;370(6512):89-94. PubMed PMID: 32753554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. AU - Mateus,Jose, AU - Grifoni,Alba, AU - Tarke,Alison, AU - Sidney,John, AU - Ramirez,Sydney I, AU - Dan,Jennifer M, AU - Burger,Zoe C, AU - Rawlings,Stephen A, AU - Smith,Davey M, AU - Phillips,Elizabeth, AU - Mallal,Simon, AU - Lammers,Marshall, AU - Rubiro,Paul, AU - Quiambao,Lorenzo, AU - Sutherland,Aaron, AU - Yu,Esther Dawen, AU - da Silva Antunes,Ricardo, AU - Greenbaum,Jason, AU - Frazier,April, AU - Markmann,Alena J, AU - Premkumar,Lakshmanane, AU - de Silva,Aravinda, AU - Peters,Bjoern, AU - Crotty,Shane, AU - Sette,Alessandro, AU - Weiskopf,Daniela, Y1 - 2020/08/04/ PY - 2020/06/25/received PY - 2020/07/30/accepted PY - 2020/8/6/pubmed PY - 2020/10/22/medline PY - 2020/8/6/entrez SP - 89 EP - 94 JF - Science (New York, N.Y.) JO - Science VL - 370 IS - 6512 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32753554/Selective_and_cross_reactive_SARS_CoV_2_T_cell_epitopes_in_unexposed_humans_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=32753554 DB - PRIME DP - Unbound Medicine ER -