دورية أكاديمية
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A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses.

التفاصيل البيبلوغرافية
العنوان: A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses.
المؤلفون: Buckley PR; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.; MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK., Lee CH; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.; MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK., Antanaviciute A; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.; MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK., Simmons A; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK., Koohy H; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.; MRC WIMM Centre for Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.; Alan Turing Fellow in Health and Medicine.
المصدر: Immunotherapy advances [Immunother Adv] 2023 Mar 15; Vol. 3 (1), pp. ltad005. Date of Electronic Publication: 2023 Mar 15 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101776979 Publication Model: eCollection Cited Medium: Internet ISSN: 2732-4303 (Electronic) Linking ISSN: 27324303 NLM ISO Abbreviation: Immunother Adv Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Oxford] : Oxford University Press, [2021]-
مستخلص: T cell recognition of SARS-CoV-2 antigens after vaccination and/or natural infection has played a central role in resolving SARS-CoV-2 infections and generating adaptive immune memory. However, the clinical impact of SARS-CoV-2-specific T cell responses is variable and the mechanisms underlying T cell interaction with target antigens are not fully understood. This is especially true given the virus' rapid evolution, which leads to new variants with immune escape capacity. In this study, we used the Omicron variant as a model organism and took a systems approach to evaluate the impact of mutations on CD8+ T cell immunogenicity. We computed an immunogenicity potential score for each SARS-CoV-2 peptide antigen from the ancestral strain and Omicron, capturing both antigen presentation and T cell recognition probabilities. By comparing ancestral vs. Omicron immunogenicity scores, we reveal a divergent and heterogeneous landscape of impact for CD8+ T cell recognition of mutated targets in Omicron variants. While T cell recognition of Omicron peptides is broadly preserved, we observed mutated peptides with deteriorated immunogenicity that may assist breakthrough infection in some individuals. We then combined our scoring scheme with an in silico mutagenesis, to characterise the position- and residue-specific theoretical mutational impact on immunogenicity. While we predict many escape trajectories from the theoretical landscape of substitutions, our study suggests that Omicron mutations in T cell epitopes did not develop under cell-mediated pressure. Our study provides a generalisable platform for fostering a deeper understanding of existing and novel variant impact on antigen-specific vaccine- and/or infection-induced T cell immunity.
Competing Interests: H.K. provides consultancy on spatiotemporal dynamics of antigen-specific cellular immunity.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)
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معلومات مُعتمدة: MC_UU_00008/7 United Kingdom MRC_ Medical Research Council; MC_UU_12010/7 United Kingdom MRC_ Medical Research Council; MC_UU_00036/1 United Kingdom MRC_ Medical Research Council; MR/S036377/1 United Kingdom MRC_ Medical Research Council; MC_PC_MR/S025952/1 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: CD8 T cell response; SARS-CoV-2; T cell recognition potential; immunogenicity; machine-learning; systems immunology
تواريخ الأحداث: Date Created: 20230421 Latest Revision: 20240313
رمز التحديث: 20240313
مُعرف محوري في PubMed: PMC10112682
DOI: 10.1093/immadv/ltad005
PMID: 37082106
قاعدة البيانات: MEDLINE
الوصف
تدمد:2732-4303
DOI:10.1093/immadv/ltad005