Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1784589148215050240 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8541101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT huwei specificcd8tcrrepertoirerecognizingconservedantigensofsarscov2inunexposedpopulationaprerequisiteforbroadspectrumcd8tcellimmunity AT hemeifang specificcd8tcrrepertoirerecognizingconservedantigensofsarscov2inunexposedpopulationaprerequisiteforbroadspectrumcd8tcellimmunity AT wangxiaoning specificcd8tcrrepertoirerecognizingconservedantigensofsarscov2inunexposedpopulationaprerequisiteforbroadspectrumcd8tcellimmunity AT sunqiang specificcd8tcrrepertoirerecognizingconservedantigensofsarscov2inunexposedpopulationaprerequisiteforbroadspectrumcd8tcellimmunity AT kuangming specificcd8tcrrepertoirerecognizingconservedantigensofsarscov2inunexposedpopulationaprerequisiteforbroadspectrumcd8tcellimmunity |