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Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules.
Nersisyan, Stepan; Zhiyanov, Anton; Zakharova, Maria; Ishina, Irina; Kurbatskaia, Inna; Mamedov, Azad; Galatenko, Alexei; Shkurnikov, Maxim; Gabibov, Alexander; Tonevitsky, Alexander.
Afiliación
  • Nersisyan S; Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
  • Zhiyanov A; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  • Zakharova M; Institute of Molecular Biology, The National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.
  • Ishina I; Armenian Bioinformatics Institute (ABI), Yerevan, Armenia.
  • Kurbatskaia I; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  • Mamedov A; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  • Galatenko A; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  • Shkurnikov M; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  • Gabibov A; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  • Tonevitsky A; Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
PeerJ ; 10: e13354, 2022.
Article en En | MEDLINE | ID: mdl-35502206
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 both because of the Omicron BA.1 mutations (N211 deletion, L212I substitution and EPE 212-214 insertion) and the Omicron BA.2 mutations (V213G substitution). 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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Presentación de Antígeno / COVID-19 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PeerJ Año: 2022 Tipo del documento: Article País de afiliación: Rusia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Presentación de Antígeno / COVID-19 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PeerJ Año: 2022 Tipo del documento: Article País de afiliación: Rusia