Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation
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- Mary Hongying Cheng
- Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
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- She Zhang
- Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
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- Rebecca A. Porritt
- Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
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- Magali Noval Rivas
- Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
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- Lisa Paschold
- Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
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- Edith Willscher
- Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
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- Mascha Binder
- Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
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- Moshe Arditi
- Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
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- Ivet Bahar
- Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
抄録
<jats:title>Significance</jats:title><jats:p>A hyperinflammatory syndrome reminiscent of toxic shock syndrome (TSS) is observed in severe COVID-19 patients, including children with Multisystem Inflammatory Syndrome in Children (MIS-C). TSS is typically caused by pathogenic superantigens stimulating excessive activation of the adaptive immune system. We show that SARS-CoV-2 spike contains sequence and structure motifs highly similar to those of a bacterial superantigen and may directly bind T cell receptors. We further report a skewed T cell receptor repertoire in COVID-19 patients with severe hyperinflammation, in support of such a superantigenic effect. Notably, the superantigen-like motif is not present in other SARS family coronaviruses, which may explain the unique potential for SARS-CoV-2 to cause both MIS-C and the cytokine storm observed in adult COVID-19.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 117 (41), 25254-25262, 2020-09-28
Proceedings of the National Academy of Sciences
