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SARS-CoV-2-specific T cell responses in patients with multisystem inflammatory syndrome in children
Ki Pui Lam1, Marcos Chiñas2, Amélie M Julé3
1Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections that occurs in the pediatric population. We sought to characterize T cell responses in MIS-C compared to COVID-19 and pediatric hyperinflammatory syndromes. MIS-C was distinct from COVID-19 and hyperinflammatory syndromes due to an expansion of T cells expressing TRBV11-2 that was not associated with HLA genotype. Children diagnosed with MIS-C, but who were negative for SARS-CoV-2 by PCR and serology, did not display Vβ skewing. There was no difference in the proportion of T cells that became activated after stimulation with SARS-CoV-2 peptides in children with MIS-C compared to convalescent COVID-19. The frequency of SARS-CoV-2-specific TCRs and the antigens recognized by these TCRs were comparable in MIS-C and COVID-19. Expansion of Vβ11-2+ T cells was a specific biomarker of MIS-C patients with laboratory confirmed SARS-CoV-2 infections. Children with MIS-C had robust antigen-specific T cell responses to SARS-CoV-2.
Insights
Multisystem inflammatory syndrome in children (MIS-C) is linked to SARS-CoV-2. A specific T cell marker, TRBV11-2, helps identify MIS-C in children with confirmed infections.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Virology
Background:
- Multisystem inflammatory syndrome in children (MIS-C) is a severe condition following SARS-CoV-2 infection.
- Understanding T cell responses is crucial for differentiating MIS-C from other inflammatory conditions in children.
Purpose of the Study:
- To characterize T cell responses in MIS-C compared to COVID-19 and other pediatric hyperinflammatory syndromes.
- To identify specific T cell biomarkers for MIS-C.
Main Methods:
- Comparative analysis of T cell receptor (TCR) Vβ repertoire, specifically TRBV11-2 expression.
- Assessment of T cell activation following stimulation with SARS-CoV-2 peptides.
- Evaluation of SARS-CoV-2 PCR and serology in MIS-C patients.
Main Results:
- MIS-C showed a distinct expansion of TRBV11-2 expressing T cells, unrelated to HLA genotype.
- Children with MIS-C but negative SARS-CoV-2 tests lacked this Vβ skewing.
- T cell activation and SARS-CoV-2-specific TCR frequencies were similar in MIS-C and convalescent COVID-19.
- TRBV11-2+ T cell expansion was a specific biomarker for MIS-C with confirmed SARS-CoV-2 infection.
Conclusions:
- Expansion of TRBV11-2+ T cells is a specific biomarker for MIS-C in SARS-CoV-2 infected children.
- MIS-C patients exhibit robust antigen-specific T cell responses to SARS-CoV-2.
- This finding aids in distinguishing MIS-C from other pediatric inflammatory conditions post-SARS-CoV-2.
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