SARS-CoV-2 spike does not interact with the T cell receptor or directly activate T cells.

Autor:	Gaglione SA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Rosales TJ; Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46556.; Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46556., Schmidt-Hong L; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139., Baker BM; Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46556.; Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46556., Birnbaum ME; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 30; Vol. 121 (31), pp. e2406615121. Date of Electronic Publication: 2024 Jul 23.
DOI:	10.1073/pnas.2406615121
Abstrakt:	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. Competing Interests: Competing interests statement:M.E.B. is a founder and consultant of Kelonia Therapeutics and Abata Therapeutics. M.E.B. is an equity holder of Kelonia Therapeutics, Abata Therapeutics, and 3T Biosciences. The lentiviral targeting approach in this manuscript is the subject of US patent applications with M.E.B. and S.A.G. as coinventors.
Databáze:	MEDLINE
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