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Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8(+) T cell immunity to wide range of epitopes, could he...

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Autores principales: Hu, Wei, He, Meifang, Wang, Xiaoning, Sun, Qiang, Kuang, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541101/
https://www.ncbi.nlm.nih.gov/pubmed/34696201
http://dx.doi.org/10.3390/vaccines9101093
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author Hu, Wei
He, Meifang
Wang, Xiaoning
Sun, Qiang
Kuang, Ming
author_facet Hu, Wei
He, Meifang
Wang, Xiaoning
Sun, Qiang
Kuang, Ming
author_sort Hu, Wei
collection PubMed
description Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8(+) T cell immunity to wide range of epitopes, could help translational efforts to improve coronavirus disease 2019 (COVID-19) prevention and therapy. However, there have been few direct studies in which such immunity exists in a population. Methods: We selected SARS-CoV-2-conserved structural peptides that are not prone to mutation as antigens for broad-spectrum CD8(+) T cell immunity. Peripheral blood mononuclear cells (PBMCs) from unexposed healthy donors were stimulated with these peptides in vitro and CD8(+) T cell-specific response was monitored. The conserved peptide-specific CD8(+) T cells were sorted for T cell receptor (TCR) repertoire sequencing. The presence of specific complementary determining region 3 (CDR3) clones was analyzed in a healthy cohort. Results: For each structural protein, including S, E, M, N, the conserved peptides could potentially provide the largest number of major histocompatibility complex-I (MHC-I) epitopes in the Oriental and Caucasian populations. For conserved peptides from spike (S), envelope (E), membrane (M), nucleocapsid (N) proteins, we found that there were no cross-reactive memory T cells in the unexposed individuals. Instead, their T cells contain naïve TCR repertoire recognizing these conserved peptides. Using TCR sequencing and CDR3 clustering for the conserved peptides specific T cells, we found that the recovered patients had a higher proportion of TCR repertoire similar with that of specific CD8(+) T cells in unexposed individuals. Meanwhile, CDR3 clones of the above T cells were widely present in the healthy population. Conclusions: This study provides evidence of broad-spectrum SARS-CoV-2 specific CD8(+) TCR repertoire in unexposed healthy population, which is implicated in the development and implementation of broad-spectrum vaccines against COVID-19.
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spelling pubmed-85411012021-10-24 Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity Hu, Wei He, Meifang Wang, Xiaoning Sun, Qiang Kuang, Ming Vaccines (Basel) Article Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8(+) T cell immunity to wide range of epitopes, could help translational efforts to improve coronavirus disease 2019 (COVID-19) prevention and therapy. However, there have been few direct studies in which such immunity exists in a population. Methods: We selected SARS-CoV-2-conserved structural peptides that are not prone to mutation as antigens for broad-spectrum CD8(+) T cell immunity. Peripheral blood mononuclear cells (PBMCs) from unexposed healthy donors were stimulated with these peptides in vitro and CD8(+) T cell-specific response was monitored. The conserved peptide-specific CD8(+) T cells were sorted for T cell receptor (TCR) repertoire sequencing. The presence of specific complementary determining region 3 (CDR3) clones was analyzed in a healthy cohort. Results: For each structural protein, including S, E, M, N, the conserved peptides could potentially provide the largest number of major histocompatibility complex-I (MHC-I) epitopes in the Oriental and Caucasian populations. For conserved peptides from spike (S), envelope (E), membrane (M), nucleocapsid (N) proteins, we found that there were no cross-reactive memory T cells in the unexposed individuals. Instead, their T cells contain naïve TCR repertoire recognizing these conserved peptides. Using TCR sequencing and CDR3 clustering for the conserved peptides specific T cells, we found that the recovered patients had a higher proportion of TCR repertoire similar with that of specific CD8(+) T cells in unexposed individuals. Meanwhile, CDR3 clones of the above T cells were widely present in the healthy population. Conclusions: This study provides evidence of broad-spectrum SARS-CoV-2 specific CD8(+) TCR repertoire in unexposed healthy population, which is implicated in the development and implementation of broad-spectrum vaccines against COVID-19. MDPI 2021-09-28 /pmc/articles/PMC8541101/ /pubmed/34696201 http://dx.doi.org/10.3390/vaccines9101093 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hu, Wei
He, Meifang
Wang, Xiaoning
Sun, Qiang
Kuang, Ming
Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity
title Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity
title_full Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity
title_fullStr Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity
title_full_unstemmed Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity
title_short Specific CD8(+) TCR Repertoire Recognizing Conserved Antigens of SARS-CoV-2 in Unexposed Population: A Prerequisite for Broad-Spectrum CD8(+) T Cell Immunity
title_sort specific cd8(+) tcr repertoire recognizing conserved antigens of sars-cov-2 in unexposed population: a prerequisite for broad-spectrum cd8(+) t cell immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541101/
https://www.ncbi.nlm.nih.gov/pubmed/34696201
http://dx.doi.org/10.3390/vaccines9101093
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