SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity

Carola Amormino; Valentina Tedeschi; Giorgia Paldino; Stefano Arcieri; Maria Teresa Fiorillo; Alessandro Paiardini; Loretta Tuosto; Martina Kunkl

doi:10.3390/cells11162526

SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity

Cells. 2022 Aug 15;11(16):2526. doi: 10.3390/cells11162526.

Authors

Carola Amormino^{1

2}, Valentina Tedeschi¹, Giorgia Paldino¹, Stefano Arcieri³, Maria Teresa Fiorillo¹, Alessandro Paiardini⁴, Loretta Tuosto^{1

2}, Martina Kunkl^{1

2}

Affiliations

¹ Department of Biology and Biotechnology Charles Darwin, Sapienza University, 00185 Rome, Italy.
² Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 Rome, Italy.
³ Department of Surgical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
⁴ Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00185 Rome, Italy.

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable β chain (TCRVβ) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4⁺ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.

Keywords: CD4+ T cells; MIS-C; SARS-CoV-2 spike; SEB; superantigen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / complications
Child
Humans
Receptors, Antigen, T-Cell, alpha-beta
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Superantigens*
Systemic Inflammatory Response Syndrome

Substances

Receptors, Antigen, T-Cell, alpha-beta
Spike Glycoprotein, Coronavirus
Superantigens
spike protein, SARS-CoV-2

Supplementary concepts

pediatric multisystem inflammatory disease, COVID-19 related

Grants and funding

This research was funded by “Sapienza University of Rome, Progetto Ateneo” to L.T and M.T.F., “FISM—Fondazione Italiana Sclerosi Multipla—FISM 2020-R-Single/001” to L.T., AIRC (Italian Association for Cancer Research), grant number MFAG 20447 to A.P., and “Ceschina Foundation” to M.T.F.