{"doi":"10.1101/2020.11.09.372169","title":"Identification of a unique TCR repertoire, consistent with a superantigen selection process in Children with Multi-system Inflammatory Syndrome","abstract":"Summary 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 Vβ-chains results in Vβ-skewing, whereby T cells with specific Vβ-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. In silico modelling indicates that polyacidic residues in TCR Vβ11-2 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. Highlights 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 TRBV11-2 skewing correlates with MIS-C severity and cytokine storm J gene/CDR3 diversity in MIS-C patients is compatible with a superantigen selection process In silico modelling indicates TCR Vβ11-2 engages in CDR3-independent interactions with the polybasic insert P 681 RRAR in the SAg-like motif of SARS-CoV-2 spike","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119663,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":231572,"name":"Lisa Paschold","orcid":"0000-0003-0020-1315","position":1,"is_corresponding":false},{"id":231571,"name":"Magali Noval Rivas","orcid":"0000-0001-5570-8928","position":2,"is_corresponding":false},{"id":231568,"name":"Mary Hongying Cheng","orcid":"0000-0001-5833-8221","position":3,"is_corresponding":false},{"id":243044,"name":"Lael M. Yonker","orcid":"0000-0003-1711-8227","position":4,"is_corresponding":false},{"id":556543,"name":"Harsha Chandnani","orcid":null,"position":5,"is_corresponding":false},{"id":556544,"name":"Merrick Lopez","orcid":null,"position":6,"is_corresponding":false},{"id":555556,"name":"Donjetë Simnica","orcid":"0000-0003-2286-1381","position":7,"is_corresponding":false},{"id":555557,"name":"Christoph Schultheiß","orcid":"0000-0001-9789-5776","position":8,"is_corresponding":false},{"id":555558,"name":"Chintda Santiskulvong","orcid":"0000-0002-4762-991X","position":9,"is_corresponding":false},{"id":112291,"name":"Jennifer E. Van Eyk","orcid":"0000-0001-9050-148X","position":10,"is_corresponding":false},{"id":227641,"name":"Alessio Fasano","orcid":"0000-0002-2134-0261","position":11,"is_corresponding":false},{"id":110068,"name":"İvet Bahar","orcid":"0000-0001-9959-4176","position":12,"is_corresponding":false},{"id":231574,"name":"Mascha Binder","orcid":"0000-0003-0663-3004","position":13,"is_corresponding":false},{"id":231575,"name":"Moshe Arditi","orcid":"0000-0001-9042-2909","position":14,"is_corresponding":false},{"id":231570,"name":"Rebecca A. Porritt","orcid":"0000-0002-0973-5092","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:13.002105Z","pmid":"33200133","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}