ArticleThe Journal of clinical investigation2021
HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
120 citing papers in PubMed, 189 citations in OpenAlex.
- Characterization of SARS-CoV-2 and common cold coronavirus-specific T-cell responses in MIS-C and Kawasaki disease children.European journal of immunology · 2022Trial
- Neurological and Neuropsychiatric Manifestations of Pediatric Inflammatory Multisystem Syndrome (PIMS/MIS-C): A Narrative Review.Journal of personalized medicine · 2026Review
- Shared TCR Vβ21.3+ T cell immunological signature between MIS-A and MIS-C.Journal of human immunity · 2026Article
- Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Cytokine and Whole-Genome Sequence Analysis in Korean Patients With Multisystem Inflammatory Syndrome in Children.Journal of Korean medical science · 2025Article
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- Polyclonal Vβ21.3 expansion in multisystem inflammatory syndrome in children despite SARS-CoV-2 vaccination.RMD open · 2025Article
- Review
- The Etiopathogenesis of Kawasaki Disease: Evolving Understanding of Diverse Triggers.Immunity, inflammation and disease · 2025Review
- Unravelling γδ T-cell dysregulation in the gut and its implications for immune-mediated diseases.Disease models & mechanisms · 2025Article
- Article
- In depth characterisation of the proteome of MIS-C and post COVID-19 infection in children reveals inflammatory pathway activation and evidence of tissue damage.Journal of translational medicine · 2025Article
- Article
- Article
- An Update on Multi-System Inflammatory Syndrome in Children.Current rheumatology reports · 2025Review
- Human genetic and immunological determinants of SARS-CoV-2 infection and multisystem inflammatory syndrome in children.Clinical and experimental immunology · 2025Review
- Distinctive T-cell receptor repertoire in paediatric inflammatory multisystem syndrome temporally associated with coronavirus disease 2019/multisystem inflammatory syndrome in children patients: possible thymus involvement.Clinical and experimental immunology · 2025Article
- Inflammatory Heart Disease in Multisystem Inflammatory Syndrome.Current cardiology reports · 2025Review
- The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells.Communications biology · 2025Article
- Multisystem inflammatory syndrome in children and Kawasaki disease.Frontiers in immunology · 2025Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.