Identification of a unique TCR repertoire, consistent with a superantigen selection process in Children with Multi-system Inflammatory Syndrome

• Published in: bioRxiv 2020-11
• Main Authors: Porritt, Rebecca A, Paschold, Lisa, Noval Rivas, Magali, Hongying Cheng, Mary, Yonker, Lael M, Chandnani, Harsha, Lopez, Merrick, Simnica, Donjete, Schultheiß, Christoph, Santiskulvong, Chintda, Van Eyk, Jennifer, Fasano, Alessio, Bahar, Ivet, Binder, Mascha, Arditi, Moshe
• Format: Article
• Language: English
• Subjects: Children; Complementarity-determining region 3; Cytokine storm; Cytokines; Genetic diversity; Inflammatory diseases; J gene; Lymphocytes T; Multisystem inflammatory syndrome in children; Septic shock; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Superantigens; T cell receptors; Toxic shock syndrome
• ISSN: 2692-8205
• DOI: 10.1101/2020.11.09.372169

Multisystem Inflammatory Syndrome in Children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares many clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. The superantigen specificity for binding different Vβ-chains results in Vβ-skewing, whereby T cells with specific Vβ-chains and diverse antigen specificity are overrepresented in the TCR repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCR Βeta Variable gene (TRBV)11-2. Furthermore, TRBV11-2 skewing was remarkably correlated with MIS-C severity and serum cytokine levels. Further analysis of TRBJ gene usage and CDR3 length distribution of MIS-C expanding TRBV11-2 clones revealed extensive junctional diversity, indicating a superantigen-mediated selection process for TRBV expansion. modelling indicates that polyacidic residues in TCR Vβ11-2 engage in strong interactions with the superantigen-like motif of SARS-CoV-2 spike glycoprotein. Overall, our data indicate that the immune response in MIS-C is consistent with superantigenic activation.