SARS-CoV-2-specific CD8+ T Cell Responses in Convalescent COVID-19 Individuals

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2021 Jan 11

PMID 33427749

Citations 163

Authors

Hassen Kared

Andrew D Redd

Evan M Bloch

Tania S Bonny

Hermi Sumatoh

Faris Kairi

Daniel Carbajo

Brian Abel

Evan W Newell

Maria P Bettinotti

Sarah E Benner

Eshan U Patel

Kirsten Littlefield

Oliver Laeyendecker

Shmuel Shoham

David Sullivan

Arturo Casadevall

Andrew Pekosz

Alessandra Nardin

Michael Fehlings

Aaron Ar Tobian

Thomas C Quinn

Affiliations

Soon will be listed here.

Abstract

Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection.

Citing Articles

Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS-CoV-2-Specific CD8 T Cell Responses.

van den Dijssel J, Konijn V, Duurland M, de Jongh R, Koets L, Veldhuisen B Eur J Immunol. 2025; 55(3):e202451565.

PMID: 40071711 PMC: 11898545. DOI: 10.1002/eji.202451565.

Mutational pressure promotes release of public CD8 T cell epitopes by proteasome from SARS-CoV-2 RBD of Omicron and its current lineages.

Kudriaeva A, Butenko I, Saratov G, Ri M, Mokrushina Y, Bondarev A iScience. 2025; 28(3):111873.

PMID: 40060909 PMC: 11889684. DOI: 10.1016/j.isci.2025.111873.

Skin patch delivery of a SARS-CoV-2 spike DNA vaccine produces broad neutralising antibody responses.

McMillan C, Corner A, Wijesundara D, Choo J, Pittayakhajonwut D, Poredi I Heliyon. 2025; 11(4):e42533.

PMID: 40034315 PMC: 11872540. DOI: 10.1016/j.heliyon.2025.e42533.

Features of Highly Homologous T-Cell Receptor Repertoire in the Immune Response to Mutations in Immunogenic Epitopes.

Zornikova K, Dianov D, Ivanova N, Davydova V, Nenasheva T, Fefelova E Int J Mol Sci. 2024; 25(23).

PMID: 39684303 PMC: 11641755. DOI: 10.3390/ijms252312591.

T cell epitope mapping reveals immunodominance of evolutionarily conserved regions within SARS-CoV-2 proteome.

Bozkus C, Brown M, Velazquez L, Thomas M, Wilson E, ODonnell T bioRxiv. 2024; .

PMID: 39484455 PMC: 11527131. DOI: 10.1101/2024.10.23.619918.

References

Elsaesser H, Sauer K, Brooks D . IL-21 is required to control chronic viral infection. Science. 2009; 324(5934):1569-72. PMC: 2830017. DOI: 10.1126/science.1174182. View

Pizzolla A, Nguyen T, Smith J, Brooks A, Kedzieska K, Heath W . Resident memory CD8 T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci Immunol. 2017; 2(12). DOI: 10.1126/sciimmunol.aam6970. View

Mahnke Y, Brodie T, Sallusto F, Roederer M, Lugli E . The who's who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013; 43(11):2797-809. DOI: 10.1002/eji.201343751. View

Neidleman J, Luo X, Frouard J, Xie G, Gill G, Stein E . SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential. Cell Rep Med. 2020; 1(6):100081. PMC: 7437502. DOI: 10.1016/j.xcrm.2020.100081. View

Yu J, Tostanoski L, Peter L, Mercado N, McMahan K, Mahrokhian S . DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020; 369(6505):806-811. PMC: 7243363. DOI: 10.1126/science.abc6284. View

Fehlings M, Simoni Y, Penny H, Becht E, Loh C, Gubin M . Author Correction: Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8 T cells. Nat Commun. 2018; 9(1):3000. PMC: 6062571. DOI: 10.1038/s41467-018-05468-y. View

Bert N, Tan A, Kunasegaran K, Tham C, Hafezi M, Chia A . SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020; 584(7821):457-462. DOI: 10.1038/s41586-020-2550-z. View

Bloch E, Shoham S, Casadevall A, Sachais B, Shaz B, Winters J . Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest. 2020; 130(6):2757-2765. PMC: 7259988. DOI: 10.1172/JCI138745. View

Patel E, Bloch E, Clarke W, Hsieh Y, Boon D, Eby Y . Comparative Performance of Five Commercially Available Serologic Assays To Detect Antibodies to SARS-CoV-2 and Identify Individuals with High Neutralizing Titers. J Clin Microbiol. 2020; 59(2). PMC: 8111143. DOI: 10.1128/JCM.02257-20. View

10.

Ferretti A, Kula T, Wang Y, Nguyen D, Weinheimer A, Dunlap G . Unbiased Screens Show CD8 T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein. Immunity. 2020; 53(5):1095-1107.e3. PMC: 7574860. DOI: 10.1016/j.immuni.2020.10.006. View

11.

Kared H, Fabre T, Bedard N, Bruneau J, Shoukry N . Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C. PLoS Pathog. 2013; 9(6):e1003422. PMC: 3688567. DOI: 10.1371/journal.ppat.1003422. View

12.

Folegatti P, Ewer K, Aley P, Angus B, Becker S, Belij-Rammerstorfer S . Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020; 396(10249):467-478. PMC: 7445431. DOI: 10.1016/S0140-6736(20)31604-4. View

13.

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin J, Olsson A . Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183(1):158-168.e14. PMC: 7427556. DOI: 10.1016/j.cell.2020.08.017. View

14.

Fehlings M, Jhunjhunwala S, Kowanetz M, OGorman W, Hegde P, Sumatoh H . Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment. J Immunother Cancer. 2019; 7(1):249. PMC: 6740011. DOI: 10.1186/s40425-019-0695-9. View

15.

Prachar M, Justesen S, Steen-Jensen D, Thorgrimsen S, Jurgons E, Winther O . Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools. Sci Rep. 2020; 10(1):20465. PMC: 7686376. DOI: 10.1038/s41598-020-77466-4. View

16.

Long Q, Tang X, Shi Q, Li Q, Deng H, Yuan J . Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020; 26(8):1200-1204. DOI: 10.1038/s41591-020-0965-6. View

17.

Grifoni A, Weiskopf D, Ramirez S, Mateus J, Dan J, Rydyznski Moderbacher C . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181(7):1489-1501.e15. PMC: 7237901. DOI: 10.1016/j.cell.2020.05.015. View

18.

Guan W, Ni Z, Hu Y, Liang W, Ou C, He J . Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020; 382(18):1708-1720. PMC: 7092819. DOI: 10.1056/NEJMoa2002032. View

19.

Newell E, Sigal N, Nair N, Kidd B, Greenberg H, Davis M . Combinatorial tetramer staining and mass cytometry analysis facilitate T-cell epitope mapping and characterization. Nat Biotechnol. 2013; 31(7):623-9. PMC: 3796952. DOI: 10.1038/nbt.2593. View

20.

Benner S, Patel E, Laeyendecker O, Pekosz A, Littlefield K, Eby Y . SARS-CoV-2 Antibody Avidity Responses in COVID-19 Patients and Convalescent Plasma Donors. J Infect Dis. 2020; 222(12):1974-1984. PMC: 7499592. DOI: 10.1093/infdis/jiaa581. View