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How to Identify SARS-CoV-2 Virus Derived Peptides

Posted by Yuri Poluektov on Nov 19, 2020 12:00:00 PM

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.

Free Manuscript Download Here

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

 

Topics: Tetramer, QuickSwitch, SARS-CoV-2

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