Comments on "An insertion unique to SARS-CoV-2 exhibits super antigenic character strengthened by recent mutations" by Cheng MH et al. 2020

Abstract

Description: This pre-print research paper reports [5] an informative experimental study related to the causative factors of the Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (CoViD-19) in children with recent SARS-CoV-2 infection. MIS-C, like CoViD-19 in adults, presents with life-threatening symptoms of hypotension, multi-organ collapse, and elevated inflammatory markers. The authors noted that the escalation of the cytotoxic adaptive immune response triggered upon super-antigen (S-Ag) presented as non-self by MHC Class-II to T cell receptors (TcRs) resembles the toxic shock syndrome. They therefore tested the hypothesis that the spike protein, S, of SARS-CoV-2 is endowed with SAg activity. The findings of structure-based computational modeling showed that S presents a high-affinity motif for, and interacts closely with both the complementarity-determining regions of the variable domains for both the α-and β-chains of TcR. Further examination determined that the S binding epitope harbors a sequence motif unique to SARS-CoV-2, and not expressed in the preceding SARS-CoV, MERS or any member of the Corona virus family tested. The S motif is similar in both sequence and structure to bacterial SAg , and has a selected-residues motif within its interfacial region that mimics the intracellular adhesion molecule (ICAM). ICAM's are molecules of the immunoglobulin super-family that play an important role in inflammation, cell-mediated immune responses in general, and in intracellular signaling events [1]. The data further indicated that TcR-SARS-CoV-2 interaction appears to vary among mutated strains [2], and that it is stronger with the European mutation (D839Y/N/E) compared to the original Asian strain. Moreover, in silico modeling revealed that the SAg motif encoded by SARS-CoV-2 is located near its S1/S2 cleavage site, a region that is remarkably similar in structure to the staphylococcal entero-toxins B SAg motif. That specific SAg interacts with both TcR and CD28, which provide co-stimulatory signals required for T cell