tetano
Editor, Senior Moderator
PLoS One
. 2022 Oct 27;17(10):e0274289.
doi: 10.1371/journal.pone.0274289. eCollection 2022.
Distorted TCR repertoires define multisystem inflammatory syndrome in children
Amna Malik[SUP] 1 [/SUP], Eszter N Tóth[SUP] 2 [/SUP], Michelle S Teng[SUP] 2 [/SUP], Jacob Hurst[SUP] 2 [/SUP], Eleanor Watt[SUP] 3 [/SUP], Lauren Wise[SUP] 4 [/SUP], Natalie Kent[SUP] 4 [/SUP], Jack Bartram[SUP] 5 [/SUP], Louis Grandjean[SUP] 6 [/SUP], Margarita Dominguez-Villar[SUP] 7 [/SUP], Stuart Adams[SUP] 4 [/SUP], Nichola Cooper[SUP] 1 [/SUP]
Affiliations
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.
. 2022 Oct 27;17(10):e0274289.
doi: 10.1371/journal.pone.0274289. eCollection 2022.
Distorted TCR repertoires define multisystem inflammatory syndrome in children
Amna Malik[SUP] 1 [/SUP], Eszter N Tóth[SUP] 2 [/SUP], Michelle S Teng[SUP] 2 [/SUP], Jacob Hurst[SUP] 2 [/SUP], Eleanor Watt[SUP] 3 [/SUP], Lauren Wise[SUP] 4 [/SUP], Natalie Kent[SUP] 4 [/SUP], Jack Bartram[SUP] 5 [/SUP], Louis Grandjean[SUP] 6 [/SUP], Margarita Dominguez-Villar[SUP] 7 [/SUP], Stuart Adams[SUP] 4 [/SUP], Nichola Cooper[SUP] 1 [/SUP]
Affiliations
- PMID: 36301874
- DOI: 10.1371/journal.pone.0274289
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.