TY - JOUR
T1 - Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals
AU - Grifoni, Alba
AU - Weiskopf, Daniela
AU - Ramirez, Sydney I.
AU - Mateus, Jose
AU - Dan, Jennifer M.
AU - Moderbacher, Carolyn Rydyznski
AU - Rawlings, Stephen A.
AU - Sutherland, Aaron
AU - Premkumar, Lakshmanane
AU - Jadi, Ramesh S.
AU - Marrama, Daniel
AU - de Silva, Aravinda M.
AU - Frazier, April
AU - Carlin, Aaron F.
AU - Greenbaum, Jason A.
AU - Peters, Bjoern
AU - Krammer, Florian
AU - Smith, Davey M.
AU - Crotty, Shane
AU - Sette, Alessandro
N1 - Funding Information:
We would like to thank Cheryl Kim, director of the LJI flow cytometry core facility for outstanding expertise. We thank Prof. Peter Kim, Abigail Powell, PhD, and colleagues (Stanford) for RBD protein synthesized from Prof. Florian Krammer (Mt. Sinai) constructs. J.M. was supported by PhD student fellowships from the Departamento Administrativo de Ciencia , Tecnología e Innovación (COLCIENCIAS) , and Pontificia Universidad Javeriana . This work was funded by the NIH NIAID under awards AI42742 ( Cooperative Centers for Human Immunology ) (S.C. and A.S.), National Institutes of Health contract Nr. 75N9301900065 (A.S. and D.W.), and U19 AI118626 (A.S. and B.P.). The BD FACSymphony purchase was partially funded by the Bill and Melinda Gates Foundation and LJI Institutional Funds (S.C. and A.S.). This work was additionally supported in part by the Johnathan and Mary Tu Foundation (D.M.S.), the NIAID under K08 award AI135078 (J.D.), and UCSD T32s AI007036 and AI007384 Infectious Diseases Division (S.I.R. and S.A.R.).
Funding Information:
We would like to thank Cheryl Kim, director of the LJI flow cytometry core facility for outstanding expertise. We thank Prof. Peter Kim, Abigail Powell, PhD, and colleagues (Stanford) for RBD protein synthesized from Prof. Florian Krammer (Mt. Sinai) constructs. J.M. was supported by PhD student fellowships from the Departamento Administrativo de Ciencia, Tecnologi?a e Innovacio?n (COLCIENCIAS), and Pontificia Universidad Javeriana. This work was funded by the NIH NIAID under awards AI42742 (Cooperative Centers for Human Immunology) (S.C. and A.S.), National Institutes of Health contract Nr. 75N9301900065 (A.S. and D.W.), and U19 AI118626 (A.S. and B.P.). The BD FACSymphony purchase was partially funded by the Bill and Melinda Gates Foundation and LJI Institutional Funds (S.C. and A.S.). This work was additionally supported in part by the Johnathan and Mary Tu Foundation (D.M.S.), the NIAID under K08 award AI135078 (J.D.), and UCSD T32s AI007036 and AI007384 Infectious Diseases Division (S.I.R. and S.A.R.). Conceptualization, A.G. D.W. S.C. and A.S.; Investigation, A.G. D.W. J.M. C.R.M. J.M.D. D.M. L.P. R.S.J. A.S. and D.W.; Formal Analysis, A.G. D.W. C.R.M. J.M.D. J.M. and S.C.; Resources, S.I.R. S.A.R. D.M.S. A.F.C. F.K. S.C. and A.S.; Data Curation, J.A.G. and B.P.; Writing, S.C. A.S. A.G. and D.W.; Supervision, B.P. A.M.d.S. S.C. and A.S.; Project Administration, A.F.; Funding Acquisition, S.C. A.S. D.W. D.S. and J.D. The authors declare no competing interests.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6/25
Y1 - 2020/6/25
N2 - Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide “megapools,” circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%–27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%–60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2.
AB - Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide “megapools,” circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%–27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%–60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2.
KW - CD4
KW - CD8
KW - COVID-19
KW - SARS-CoV-2
KW - T cells
KW - coronavirus
KW - cross-reactivity
KW - epitopes
UR - http://www.scopus.com/inward/record.url?scp=85085363958&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.05.015
DO - 10.1016/j.cell.2020.05.015
M3 - Article
C2 - 32473127
AN - SCOPUS:85085363958
SN - 0092-8674
VL - 181
SP - 1489-1501.e15
JO - Cell
JF - Cell
IS - 7
ER -