Distorted TCR repertoires define multisystem inflammatory syndrome in children

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....

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Bibliographic Details
Published in:PloS one 2022-10, Vol.17 (10), p.e0274289-e0274289
Main Authors: Malik, Amna, Tóth, Eszter N, Teng, Michelle S, Hurst, Jacob, Watt, Eleanor, Wise, Lauren, Kent, Natalie, Bartram, Jack, Grandjean, Louis, Dominguez-Villar, Margarita, Adams, Stuart, Cooper, Nichola
Format: Article
Language:English
Subjects:
Analysis
Antigens
Asymptomatic
Biology and Life Sciences
Biotechnology
Child health services
Children
Cloning
Comparative analysis
Complementarity-determining region 3
Computer and Information Sciences
Coronaviruses
COVID-19
Gene expression
Hypothesis testing
Infections
Lymphocytes
Lymphocytes T
Medicine and Health Sciences
Multisystem inflammatory syndrome in children
Pandemics
Patients
People and Places
Research and Analysis Methods
Respiratory diseases
Severe acute respiratory syndrome coronavirus 2
Signs and symptoms
T cell receptors
T cells
T-cell receptor
Viral diseases
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0274289