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In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape

SARS-CoV-2 variants of concern have emerged since the COVID-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antib...

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Autores principales: Pretti, Marco Antônio M., Galvani, Rômulo G., Scherer, Nicole M., Farias, Alessandro S., Boroni, Mariana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824006/
https://www.ncbi.nlm.nih.gov/pubmed/35149224
http://dx.doi.org/10.1016/j.meegid.2022.105236
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author Pretti, Marco Antônio M.
Galvani, Rômulo G.
Scherer, Nicole M.
Farias, Alessandro S.
Boroni, Mariana
author_facet Pretti, Marco Antônio M.
Galvani, Rômulo G.
Scherer, Nicole M.
Farias, Alessandro S.
Boroni, Mariana
author_sort Pretti, Marco Antônio M.
collection PubMed
description SARS-CoV-2 variants of concern have emerged since the COVID-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, little attention has been given to pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses by new lineages. In this work, we predicted SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and their potential to trigger or hinder CD8+ T cell response by using HLA binding and TCR reactivity in silico predictions. Also, we estimated the population's coverage for different lineages, which accounts for the ability to present a set of peptides based on the most frequent HLA alleles of a given population. We considered binding predictions to 110 ccClass I HLA alleles from 29 countries to investigate differences in the fraction of individuals expected to respond to a given epitope set from new and previous lineages. We observed a higher population coverage for the variant detected in the UK (B.1.1.7), and South Africa (B.1.351), as well as for the Brazilian P.1 lineage, but not P.2, compared to the reference lineage. Moreover, individual mutations such as Spike N501Y and Nucleocapsid D138Y were predicted to have an overall stronger affinity through HLA-I than the reference sequence while Spike E484K shows signs of evasion. In summary, we provided evidence for the existence of potentially immunogenic and conserved epitopes across new SARS-CoV-2 variants, but also mutant peptides exhibiting diminished or abolished HLA-I binding. It also highlights the augmented population coverage for three new lineages. Whether these changes imply more T cell reactivity or potential to evade from CD8+ T cell responses requires experimental verification.
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spelling pubmed-88240062022-02-09 In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape Pretti, Marco Antônio M. Galvani, Rômulo G. Scherer, Nicole M. Farias, Alessandro S. Boroni, Mariana Infect Genet Evol Article SARS-CoV-2 variants of concern have emerged since the COVID-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, little attention has been given to pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses by new lineages. In this work, we predicted SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and their potential to trigger or hinder CD8+ T cell response by using HLA binding and TCR reactivity in silico predictions. Also, we estimated the population's coverage for different lineages, which accounts for the ability to present a set of peptides based on the most frequent HLA alleles of a given population. We considered binding predictions to 110 ccClass I HLA alleles from 29 countries to investigate differences in the fraction of individuals expected to respond to a given epitope set from new and previous lineages. We observed a higher population coverage for the variant detected in the UK (B.1.1.7), and South Africa (B.1.351), as well as for the Brazilian P.1 lineage, but not P.2, compared to the reference lineage. Moreover, individual mutations such as Spike N501Y and Nucleocapsid D138Y were predicted to have an overall stronger affinity through HLA-I than the reference sequence while Spike E484K shows signs of evasion. In summary, we provided evidence for the existence of potentially immunogenic and conserved epitopes across new SARS-CoV-2 variants, but also mutant peptides exhibiting diminished or abolished HLA-I binding. It also highlights the augmented population coverage for three new lineages. Whether these changes imply more T cell reactivity or potential to evade from CD8+ T cell responses requires experimental verification. The Author(s). Published by Elsevier B.V. 2022-04 2022-02-08 /pmc/articles/PMC8824006/ /pubmed/35149224 http://dx.doi.org/10.1016/j.meegid.2022.105236 Text en © 2022 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Pretti, Marco Antônio M.
Galvani, Rômulo G.
Scherer, Nicole M.
Farias, Alessandro S.
Boroni, Mariana
In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
title In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
title_full In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
title_fullStr In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
title_full_unstemmed In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
title_short In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
title_sort in silico analysis of mutant epitopes in new sars-cov-2 lineages suggest global enhanced cd8+ t cell reactivity and also signs of immune response escape
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824006/
https://www.ncbi.nlm.nih.gov/pubmed/35149224
http://dx.doi.org/10.1016/j.meegid.2022.105236
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