Distorted TCR repertoires define multisystem inflammatory syndrome in children

PLoS One. 2022 Oct 27;17(10):e0274289. doi: 10.1371/journal.pone.0274289. eCollection 2022.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / genetics
  • Child
  • Connective Tissue Diseases*
  • Humans
  • Pandemics
  • Receptors, Antigen, T-Cell / genetics
  • SARS-CoV-2
  • Systemic Inflammatory Response Syndrome / diagnosis
  • Systemic Inflammatory Response Syndrome / genetics

Substances

  • Receptors, Antigen, T-Cell

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related