Published by Yuri Poluektov on
In our previous blog post (How to screen SARS-CoV-2 peptides to facilitate T cell research) we have described how the immune system samples all of the pathogenic proteins by looking at the small fragments of each protein and making a determination on whether that fragment (also referred to as peptide) belongs in the body. We have also described in our previous blog post (Find Human MHC Class I Dominant Peptides) the multiple MHC alleles that we tested for their ability to present SARS-CoV-2 peptides.
In our experiments of determining the ability of A2, A3, A11 and A24 MHC alleles to bind SARS-CoV-2 derived peptides we found little overlap between the peptides presented by human alleles and the H-2Kb mouse allele.
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. We have performed an additional study to find SARS-CoV-2 peptides that can be presented by the H-2Kb mouse MHC molecule and 2 of those peptides (VVFLHVTYV and SIIAYTMSL) also proved to be strong binders of the HLA-A*02:01 human allele.
We encourage further trials with our 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.
| H-2 Kb | 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) | + |
Summary of SARS-CoV-2 peptide binding to mouse H-2 Kb MHC molecules.
Click the link below to view a full description of 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