Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2024 Jul 30;121(31):e2406615121. doi: 10.1073/pnas.2406615121. Epub 2024 Jul 23.
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.
SARS-CoV-2 感染可引起儿童多系统炎症综合征，类似于超抗原诱导的中毒性休克综合征。最近的研究表明，SARS-CoV-2 刺突（S）蛋白可通过结合 T 细胞受体（TCR）并诱导广泛的抗原非依赖性 T 细胞反应，充当超抗原。基于结构的计算建模在 S 受体结合域附近以及与已知神经毒素同源的部位鉴定出潜在的 TCR 结合位点。我们通过实验研究了这一理论的基础机制，即 TCR 与 S 蛋白的直接相互作用。重组表达的 S 蛋白和 TCR 的表面等离子体共振未检测到可检测的结合。正交地，我们用 SARS-CoV-2 S 的野生型和预融合稳定形式假型化慢病毒，在细胞系测定中证明了它们的功能，并且没有观察到 CD8 T 细胞的转导、激活或增殖刺激。我们得出的结论是，SARS-CoV-2 刺突蛋白不太可能与 TCR 非特异性结合，也不具有超抗原特性。
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