"Our findings shed important new light on the mysteries of MIS-C," said Moshe Arditi, MD, director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai. He was corresponding and co-senior author of the study, published in the Journal of Clinical Investigation.
T cell receptor skewing also occurs in toxic shock syndrome as a reaction to so-called bacterial superantigens. To find out if a similar process was driving T cell receptor skewing in MIS-C, the investigators used computer modeling. This approach identified a potentially strong interaction between a specific T cell receptor type and a protein on SARS-CoV-2, the virus that causes COVID-19.
A prior study co-led by Arditi and Ivet Bahar, PhD, at the Pittsburgh School of Medicine discovered that a protein in SARS-CoV-2 is structured like a superantigen. Now the scientists have evidence that children who develop MIS-C have an immune response similar to that raised against superantigens.
"Future investigations are needed to characterize the phenotype and functional properties of T cells involved in this process, in order to provide a complete understanding of how MIS-C develops and progresses," said Arditi, professor of Pediatrics and Biomedical Sciences and the GUESS?/Fashion Industries Guild Chair in Community Child Health.
The other co-senior authors of the study were Bahar from the University of Pittsburgh School of Medicine, and Mascha Binder, MD, from Martin Luther University Halle-Wittenberg in Germany.
Arditi has continued to contribute to this important line of research, including a study published May 25 in the Journal of Clinical Investigation that uncovered how viral particles in the gut help instigate MIS-C.
Funding: Research reported in this publication was funded by the National Institutes of Health under award numbers P41 GM103712, R01 AI072726 and 3RO1AI072726-10S1.