Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation

Proceedings of the National Academy of Sciences of the United States of America - Tập 117 Số 41 - Trang 25254-25262 - 2020
Mary Hongying Cheng1, She Zhang1, Rebecca A. Porritt2,3, Magali Noval Rivas2,3, Lisa Paschold4, Edith Willscher4, Mascha Binder4, Moshe Arditi2,3, İvet Bahar1
1Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
2Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
3Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
4Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany

Tóm tắt

SignificanceA 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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 117 Số 41

25254-25262

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