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Distorted TCR repertoires define multisystem inflammatory syndrome in children

Malik, A; Tóth, EN; Teng, MS; Hurst, J; Watt, E; Wise, L; Kent, N; ... Cooper, N; + view all (2022) Distorted TCR repertoires define multisystem inflammatory syndrome in children. PLoS ONE , 17 (10) , Article e0274289. 10.1371/journal.pone.0274289. Green open access

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Abstract

While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with MIS-C (n = 12) and mild (n = 8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n = 8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of children with MIS-C are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines MIS-C in children.

Type: Article
Title: Distorted TCR repertoires define multisystem inflammatory syndrome in children
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0274289
Publisher version: https://doi.org/10.1371/journal.pone.0274289
Language: English
Additional information: © 2022 Malik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Child, Humans, SARS-CoV-2, COVID-19, Pandemics, Receptors, Antigen, T-Cell, Connective Tissue Diseases, Systemic Inflammatory Response Syndrome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10173988
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