In a previous blog post (How to screen SARS-CoV-2 peptides to facilitate T cell research), MBL International describes how the immune system samples all of the pathogenic proteins by looking at the small fragments of each protein and determining whether that fragment (also referred to as peptide) belongs in the body. In another blog post (Find Human MHC Class I Dominant Peptides), the multiple MHC alleles that MBL International tested for their ability to present SARS-CoV-2 peptides were described.
In the experiments carried out by MBL International to determine the ability of A2, A3, A11 and A24 MHC alleles to bind SARS-CoV-2 derived peptides, little overlap between the peptides presented by human alleles and the H-2Kb mouse allele were found.
While a purely theoretical exercise at this point, the discovery of peptide sequences that could bind a human allele, as well as a mouse allele, could become very useful should a SARS-CoV-2 mouse model become available. MBL International has performed an additional study to find SARS-CoV-2 peptides that can be presented by the H-2Kb mouse MHC molecule, and two of those peptides (VVFLHVTYV and SIIAYTMSL) also proved to be strong binders of the HLA-A*02:01 human allele.
MBL International encourages further trials with their QuickSwitch™ system to help the development of a functional SARS-CoV-2 mouse model that could lead to the creation of a robust COVID-19 vaccine.
Summary of SARS-CoV-2 peptide binding to mouse H-2 Kb MHC molecules.
| H-2Kb | HLA-A*02:01 | ||
|---|---|---|---|
| VNFNFNGL | SARS-CoV-2 Chain A, spike glycoprotein (539-546) | + | |
| MAYRFNGI | SARS-CoV-2 Chain A, spike glycoprotein (902-909) | + | |
| INITRFQTL | SARS-CoV-2 Chain A, spike glycoprotein (233-241) | + | |
| VVLSFELL | SARS-CoV-2 Chain A, spike glycoprotein (511-518) | + | |
| SIVRFPNI | SARS-CoV-2 Chain A, spike glycoprotein (325-332) | + | |
| GNYNYLYRL | SARS-CoV-2 Chain A, spike glycoprotein (447-455) | + | |
| VVFLHVTYV | SARS-CoV-2 Chain A, spike glycoprotein (1060-1068) | + | + |
| SIIAYTMSL | SARS-CoV-2 Chain A, spike glycoprotein (691-699) | + | + |
| VTQLYLGGM | SARS-CoV-2 ORF1ab polyprotein (5385-5393) | + | |
| ITGLYPTL | SARS-CoV-2 ORF1ab polyprotein (5573-5580) | + | |
| AAYYVGYL | SARS-CoV-2 Chain A, spike glycoprotein (263-270) | + | |
| YNYLYRLF | SARS-CoV-2 Chain A, spike glycoprotein (449-456) | + |
Click the link below to view a full description of the experiment from the Poluektov, Daftarian and Delcommenne manuscript.
References:
1.Yiwen Zhang et al.The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I bioRxiv 2020.05.24.111823; doi: https://doi.org/10.1101/2020.05.24.111823
2.Chao Hu et al. Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants bioRxiv 2020.11.02.364729; doi: https://doi.org/10.1101/2020.11.02.364729