Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules

  1. Stepan Nersisyan
  2. Anton Zhiyanov
  3. Maria Zakharova
  4. Irina Ishina
  5. Inna Kurbatskaia
  6. Azad Mamedov
  7. Alexey Galatenko
  8. Maxim Shkurnikov
  9. Alexander Gabibov
  10. Alexander Tonevitsky

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Abstract

The T-cell immune response is a major determinant of effective SARS-CoV-2 clearance. Here, using the recently developed T-CoV bioinformatics pipeline ( https://t-cov.hse.ru ) we analyzed the peculiarities of the viral peptide presentation for the Omicron, Delta and Wuhan variants of SARS-CoV-2. First, we showed the absence of significant differences in the presentation of SARS-CoV-2-derived peptides by the most frequent HLA class I/II alleles and the corresponding HLA haplotypes. Then, the analysis was limited to the set of peptides originating from the Spike proteins of the considered SARS-CoV-2 variants. The major finding was the destructive effect of the Omicron mutations on PINLVRDLPQGFSAL peptide, which was the only tight binder from the Spike protein for HLA-DRB1*03:01 allele and some associated haplotypes. Specifically, we predicted a dramatical decline in binding affinity of HLA-DRB1*03:01 and this peptide after N211 deletion, L212I substitution and EPE 212-214 insertion. The computational prediction was experimentally validated by ELISA with the use of corresponding thioredoxin-fused peptides and recombinant HLA-DR molecules. Another finding was the significant reduction in the number of tightly binding Spike peptides for HLA-B*07:02 HLA class I allele (both for Omicron and Delta variants). Overall, the majority of HLA alleles and haplotypes was not significantly affected by the mutations, suggesting the maintenance of effective T-cell immunity against the Omicron and Delta variants. Finally, we introduced the Omicron variant to T-CoV portal and added the functionality of haplotype-level analysis to it.

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    SciScore for 10.1101/2022.02.21.481175: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    Briefly, the genetic constructions for recombinant HLA-DR α and β (HLA-DRB1*03:01) chains with CLIP expression in in HEK293F suspension cells were created based on pFUSE vector encoding constant fragment of human immunoglobulin heavy chain (Fc).
    pFUSE
    suggested: None
    Software and Algorithms
    SentencesResources
    Briefly, HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 genes were sequenced with the MiSeq platform (Illumina, San Diego, CA, USA) using reagent kit HLA-Expert (DNA-Technology LLC, Moscow, Russia).
    MiSeq
    suggested: (A5-miseq, RRID:SCR_012148)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2022.02.21.481175v1 on bioRxiv