{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:04:08Z","timestamp":1791299048303,"version":"4.1.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["P41 GM103712"],"award-info":[{"award-number":["P41 GM103712"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI072726"],"award-info":[{"award-number":["R01 AI072726"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,10,13]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <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>","DOI":"10.1073\/pnas.2010722117","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T20:27:50Z","timestamp":1601324870000},"page":"25254-25262","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":303,"title":["Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5833-8221","authenticated-orcid":false,"given":"Mary Hongying","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-4498","authenticated-orcid":false,"given":"She","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-5092","authenticated-orcid":false,"given":"Rebecca A.","family":"Porritt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Noval Rivas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Paschold","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Oncology\/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Willscher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Oncology\/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mascha","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Oncology\/Hematology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-2909","authenticated-orcid":false,"given":"Moshe","family":"Arditi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-4176","authenticated-orcid":false,"given":"Ivet","family":"Bahar","sequence":"additional","affiliation":[{"name":"Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00749-2020"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0311-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.05.002"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31094-1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31103-X"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048360"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2013.03.012"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2606.190783"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.10369"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.435"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11030178"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.09.110193.000533"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.22.8941"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00681.x"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1117"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2507"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.169"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.5802\/crbiol.8","article-title":"A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications","volume":"343","author":"Changeux J.-P.","year":"2020","unstructured":"J.-P. Changeux, Z. Amoura, F. A. Rey, M. Miyara, A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications. C. R. Biol. 343, 33\u201339 (2020).","journal-title":"C. R. Biol."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001149"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00942"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2004.17.528"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd3871"},{"key":"e_1_3_4_25_2","unstructured":"T. Sekine . Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 10.1016\/j.cell.2020.08.017 (2020)."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","unstructured":"B. Korber . Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. bioRxiv:2020.2004.2029.069054 (15 June 2020).","DOI":"10.1101\/2020.04.29.069054"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","unstructured":"S. H. Zhan B. E. Deverman Y. A. Chan SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? bioRxiv:2020.2005.2001.073262 (21 May 2020).","DOI":"10.1101\/2020.05.01.073262"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.024"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","unstructured":"D. M. Del Valle . An inflammatory cytokine signature helps predict COVID-19 severity and death. medRxiv:10.1101\/2020.05.28.20115758 (30 May 2020).","DOI":"10.1101\/2020.05.28.20115758"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.8.5490"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.4049\/jimmunol.158.1.247","article-title":"B cell epitope mapping of the bacterial superantigen staphylococcal enterotoxin B: The dominant epitope region recognized by intravenous IgG","volume":"158","author":"Nishi J.-I.","year":"1997","unstructured":"J.-I. Nishi ., B cell epitope mapping of the bacterial superantigen staphylococcal enterotoxin B: The dominant epitope region recognized by intravenous IgG. J. Immunol. 158, 247\u2013254 (1997).","journal-title":"J. Immunol."},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601525"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01015-09"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013253"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.630715"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2020.1007.1004"},{"key":"e_1_3_4_37_2","first-page":"109","article-title":"Perspectives on the development of neutralizing antibodies against SARS-CoV-2","volume":"3","author":"Ho M.","year":"2020","unstructured":"M. Ho, Perspectives on the development of neutralizing antibodies against SARS-CoV-2. Antib. Ther. 3, 109\u2013114 (2020).","journal-title":"Antib. Ther."},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb7269"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2380-z"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0827"},{"key":"e_1_3_4_41_2","first-page":"270","article-title":"A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2","volume":"579","author":"Shi R.","year":"2020","unstructured":"R. Shi ., A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 579, 270\u2013273 (2020).","journal-title":"Nature"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6952"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2349-y"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.025"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2548-6"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.015"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","unstructured":"S. P. Weisberg Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19. medRxiv:10.1101\/2020.07.12.20151068 (14 July 2020).","DOI":"10.1101\/2020.07.12.20151068"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00510-20"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.460-463.2001"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/124.2.206"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1089\/088282403763635465"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0817-4"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007236"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407152101"},{"key":"e_1_3_4_56_2","first-page":"658","article-title":"Protein modeling by E-mail","volume":"13","author":"Peitsch M. C.","year":"1995","unstructured":"M. C. Peitsch, Protein modeling by E-mail. Bio\/technology 13, 658\u2013660 (1995).","journal-title":"Bio\/technology"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20945"},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1093\/bioinformatics\/btw514","article-title":"PRODIGY: A web server for predicting the binding affinity of protein-protein complexes","volume":"32","author":"Xue L. C.","year":"2016","unstructured":"L. C. Xue, J. P. Rodrigues, P. L. Kastritis, A. M. Bonvin, A. Vangone, PRODIGY: A web server for predicting the binding affinity of protein-protein complexes. Bioinformatics 32, 3676\u20133678 (2016).","journal-title":"Bioinformatics"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01897"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1644110"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.101030"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0903.020360"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.9.3623"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1577"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2010722117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2010722117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T21:16:22Z","timestamp":1723670182000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2010722117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,28]]},"references-count":64,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2020,10,13]]}},"alternative-id":["10.1073\/pnas.2010722117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2010722117","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.05.21.109272","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,28]]},"assertion":[{"value":"2020-09-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}