SARS-CoV-2 Spike Does Not Interact with the T Cell Receptor or Directly Activate T Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2024 Jul 23

PMID 39042676

Authors

Stephanie A Gaglione

Tatiana J Rosales

Laura Schmidt-Hong

Brian M Baker

Michael E Birnbaum

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2infection can induce multisystem inflammatory syndrome in children, which resembles superantigen-induced toxic shock syndrome. Recent work has suggested that the SARS-CoV-2 spike (S) protein could act as a superantigen by binding T cell receptors (TCRs) and inducing broad antigen-independent T cell responses. Structure-based computational modeling identified potential TCR-binding sites near the S receptor-binding domain, in addition to a site with homology to known neurotoxins. We experimentally examined the mechanism underpinning this theory-the direct interaction between the TCR and S protein. Surface plasmon resonance of recombinantly expressed S protein and TCR revealed no detectable binding. Orthogonally, we pseudotyped lentiviruses with SARS-CoV-2 S in both wild-type and prefusion-stabilized forms, demonstrated their functionality in a cell line assay, and observed no transduction, activation, or stimulation of proliferation of CD8 T cells. We conclude that it is unlikely that the SARS-CoV-2 spike protein engages nonspecifically with TCRs or has superantigenic character.

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