tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2024 Jul 30;121(31):e2406615121.
doi: 10.1073/pnas.2406615121. Epub 2024 Jul 23. SARS-CoV-2 spike does not interact with the T cell receptor or directly activate T cells
Stephanie A Gaglione[SUP] 1 2 [/SUP], Tatiana J Rosales[SUP] 3 4 [/SUP], Laura Schmidt-Hong[SUP] 2 5 [/SUP], Brian M Baker[SUP] 3 4 [/SUP], Michael E Birnbaum[SUP] 2 5 6 [/SUP]
Affiliations
Suggested edit: 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[SUP]+[/SUP] T cells. We conclude that it is unlikely that the SARS-CoV-2 spike protein engages nonspecifically with TCRs or has superantigenic character.
Keywords: SARS-CoV-2; T cell receptor; superantigen.
. 2024 Jul 30;121(31):e2406615121.
doi: 10.1073/pnas.2406615121. Epub 2024 Jul 23. SARS-CoV-2 spike does not interact with the T cell receptor or directly activate T cells
Stephanie A Gaglione[SUP] 1 2 [/SUP], Tatiana J Rosales[SUP] 3 4 [/SUP], Laura Schmidt-Hong[SUP] 2 5 [/SUP], Brian M Baker[SUP] 3 4 [/SUP], Michael E Birnbaum[SUP] 2 5 6 [/SUP]
Affiliations
- PMID: 39042676
- DOI: 10.1073/pnas.2406615121
Suggested edit: 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[SUP]+[/SUP] T cells. We conclude that it is unlikely that the SARS-CoV-2 spike protein engages nonspecifically with TCRs or has superantigenic character.
Keywords: SARS-CoV-2; T cell receptor; superantigen.