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

对新型SARS-CoV-2毒株突变表位的计算机模拟分析表明,CD8+ T细胞反应性普遍增强,并且也出现了免疫逃逸的迹象。

阅读:1

Abstract

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.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。