QuickSwitch™: a validated platform for both screening MHC binding SARS-CoV-2 peptides and making SARS-CoV-2 specific MHC class I and II tetramers.

Abstract

Abstract The success of SARS-CoV-2 vaccines is measured by their ability to mount long-lasting memory responses. To this end, it is important to identify viral protein fragments, or peptides, that generate the best immune response and lead to the development of memory T cells. For this purpose, researchers need a system that would allow them to rapidly test the ability of an antigenic peptide to be presented by the immune system and to identify T cells that can be stimulated by such a peptide in the context of the right MHC molecule. The QuickSwitch™ platform contains two modules for performing both functions. First a large number of SARS-CoV-2 peptides, including mutant peptides were incubated with QuickSwitch™ monomers or tetramers and exchanged against their exiting peptides in the first module. Peptide binding affinities to various human MHC Class I and Class II alleles, which are correlated with their exchange rates, were determined by the capture binding assay, the second QuickSwitch™ module. MHC tetramers built with SARS-CoV-2 high affinity MHC binding peptides were then used for T cell staining. Cell staining indicated that tetramers generated with the QuickSwitch™ platform were able to stain and identify T cells specific for the tested peptides. Further, peptides that bound to multiple MHC alleles, including potentially dominant peptides, were also detected. In conclusion, since QuickSwitch™ allows the screening of MHC binding SARS-CoV-2 peptides and, at the same time, the generation of corresponding tetramers, this platform is a useful tool for developing SARS-CoV-2 vaccines, monitoring T cell populations from vaccinated subjects and assessing the durability of mounted responses.