The identification of a SARs-CoV2 S2 protein-derived peptide with super-antigen-like stimulatory properties on T-cells
Tu, T. H.; Bennani, F. E.; Masroori, N.; Liu, C.; Nemati, A.; Rozza, N.; Grunbaum, A. M.; Kremer, R.; Milhalcioiu, C.; Roy, D.-C.; Rudd, C.
Show abstract
Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3). Computational modeling predicts P3 binding to sites on MHC class I/II and the TCR that partially overlap with sites for the binding of staphylococcal enterotoxins B and H. Like SEB and SEH peptides, P3 stimulated 25-40% of human CD4+ and CD8+ T cells, increasing IFN-{gamma} and granzyme B production. viSNE and SPADE profiling identified overlapping and distinct IFN-{gamma} and GZMB subsets. The super-antigenic properties of P3 were further evident by its selective expansion of T cells expressing specific TCR V and V{beta} chain repertoires. In vivo experiments in mice revealed that the administration of P3 led to a significant upregulation of proinflammatory cytokines IL-1{beta}, IL-6, and TNF-. While the clinical significance of P3 in COVID-19 remains unclear, its homology to other mammalian proteins suggests a potential role for this peptide family in human inflammation and autoimmunity.
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