{"doi":"10.1172/jci146614","title":"HLA class I–associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children","abstract":"Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. Superantigen specificity for different Vβ chains results in Vβ skewing, whereby T cells with specific Vβ chains and diverse antigen specificity are overrepresented in the T cell receptor (TCR) repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCRβ variable gene 11-2 (TRBV11-2), with up to 24% of clonal T cell space occupied by TRBV11-2 T cells, which correlated with MIS-C severity and serum cytokine levels. Analysis of TRBJ gene usage and complementarity-determining region 3 (CDR3) length distribution of MIS-C expanded TRBV11-2 clones revealed extensive junctional diversity. Patients with TRBV11-2 expansion shared HLA class I alleles A02, B35, and C04, indicating what we believe is a novel mechanism for CDR3-independent T cell expansion. In silico modeling indicated that polyacidic residues in the Vβ chain encoded by TRBV11-2 (Vβ21.3) strongly interact with the superantigen-like motif of SARS-CoV-2 spike glycoprotein, suggesting that unprocessed SARS-CoV-2 spike may directly mediate TRBV11-2 expansion. Overall, our data indicate that a CDR3-independent interaction between SARS-CoV-2 spike and TCR leads to T cell expansion and possibly activation, which may account for the clinical presentation of MIS-C.","journal":"Journal of Clinical Investigation","year":2021,"id":146790,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":194,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","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":294332,"name":"John K. McCormick","orcid":"0000-0003-3742-7289","position":11,"is_corresponding":false},{"id":227641,"name":"Alessio Fasano","orcid":"0000-0002-2134-0261","position":12,"is_corresponding":false},{"id":110068,"name":"İvet Bahar","orcid":"0000-0001-9959-4176","position":13,"is_corresponding":false},{"id":231574,"name":"Mascha Binder","orcid":"0000-0003-0663-3004","position":14,"is_corresponding":false},{"id":231575,"name":"Moshe Arditi","orcid":"0000-0001-9042-2909","position":15,"is_corresponding":false},{"id":231570,"name":"Rebecca A. Porritt","orcid":"0000-0002-0973-5092","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-18T23:42:24.567796Z","pmid":"33705359","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":[]}