SARS-CoV-2 infection 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.

中文翻译：

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SARS-CoV-2 刺突不与 T 细胞受体相互作用或直接激活 T 细胞


SARS-CoV-2感染可诱发儿童多系统炎症综合征，类似于超抗原诱发的中毒性休克综合征。最近的研究表明，SARS-CoV-2 刺突 (S) 蛋白可以通过结合 T 细胞受体 (TCR) 并诱导广泛的不依赖于抗原的 T 细胞反应来充当超级抗原。基于结构的计算模型除了与已知神经毒素具有同源性的位点外，还确定了 S 受体结合域附近潜在的 TCR 结合位点。我们通过实验检验了支撑这一理论的机制——TCR 和 S 蛋白之间的直接相互作用。重组表达的 S 蛋白和 TCR 的表面等离子共振显示没有可检测到的结合。正交地，我们用野生型和融合前稳定形式的 SARS-CoV-2 S 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 的转导、激活或增殖刺激+ T细胞。我们的结论是，SARS-CoV-2 刺突蛋白不太可能与 TCR 非特异性结合或具有超抗原特性。