{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:19:24Z","timestamp":1776269964097,"version":"3.50.1"},"posted":{"date-parts":[[2020,11,9]]},"group-title":"Immunology","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,11,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Multisystem Inflammatory Syndrome in Children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares many clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. The superantigen specificity for binding different V\u03b2-chains results in V\u03b2-skewing, whereby T cells with specific V\u03b2-chains and diverse antigen specificity are overrepresented in the TCR repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCR Beta Variable gene (TRBV)11-2. Furthermore, TRBV11-2 skewing was remarkably correlated with MIS-C severity and serum cytokine levels. Further analysis of TRBJ gene usage and CDR3 length distribution of MIS-C expanding TRBV11-2 clones revealed extensive junctional diversity, indicating a superantigen-mediated selection process for TRBV expansion.\n                  <jats:italic>In silico<\/jats:italic>\n                  modelling indicates that polyacidic residues in TCR V\u03b211-2 engage in strong interactions with the superantigen-like motif of SARS-CoV-2 spike glycoprotein. Overall, our data indicate that the immune response in MIS-C is consistent with superantigenic activation.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Multisystem Inflammatory Disease in Children (MIS-C) patients exhibit T cell receptor (TCR) repertoire skewing, with expansion of T cell Receptor Beta Variable gene (TRBV)11-2<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>TRBV11-2 skewing correlates with MIS-C severity and cytokine storm<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>J gene\/CDR3 diversity in MIS-C patients is compatible with a superantigen selection process<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>In silico<\/jats:italic>\n                        modelling indicates TCR V\u03b211-2 engages in CDR3-independent interactions with the polybasic insert P\n                        <jats:sub>681<\/jats:sub>\n                        RRAR in the SAg-like motif of SARS-CoV-2 spike\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2020.11.09.372169","type":"posted-content","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T01:45:17Z","timestamp":1604972717000},"source":"Crossref","is-referenced-by-count":11,"title":["Identification of a unique TCR repertoire, consistent with a superantigen selection process in Children with Multi-system Inflammatory Syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-5092","authenticated-orcid":false,"given":"Rebecca A","family":"Porritt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Paschold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-8928","authenticated-orcid":false,"given":"Magali Noval","family":"Rivas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5833-8221","authenticated-orcid":false,"given":"Mary Hongying","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lael M","family":"Yonker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harsha","family":"Chandnani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merrick","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donjete","family":"Simnica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Schulthei\u00df","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chintda","family":"Santiskulvong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-148X","authenticated-orcid":false,"given":"Jennifer","family":"Van Eyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-0261","authenticated-orcid":false,"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-4176","authenticated-orcid":false,"given":"Ivet","family":"Bahar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-3004","authenticated-orcid":false,"given":"Mascha","family":"Binder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-2909","authenticated-orcid":false,"given":"Moshe","family":"Arditi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080423122750000_2020.11.09.372169v1.1","unstructured":"American Academy of Pediatrics. 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