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Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution
Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264683/ https://www.ncbi.nlm.nih.gov/pubmed/37325653 http://dx.doi.org/10.3389/fimmu.2023.1130876 |
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author | Postovskaya, Anna Vujkovic, Alexandra de Block, Tessa van Petersen, Lida van Frankenhuijsen, Maartje Brosius, Isabel Bottieau, Emmanuel Van Dijck, Christophe Theunissen, Caroline van Ierssel, Sabrina H. Vlieghe, Erika Bartholomeus, Esther Mullan, Kerry Adriaensen, Wim Vanham, Guido Ogunjimi, Benson Laukens, Kris Vercauteren, Koen Meysman, Pieter |
author_facet | Postovskaya, Anna Vujkovic, Alexandra de Block, Tessa van Petersen, Lida van Frankenhuijsen, Maartje Brosius, Isabel Bottieau, Emmanuel Van Dijck, Christophe Theunissen, Caroline van Ierssel, Sabrina H. Vlieghe, Erika Bartholomeus, Esther Mullan, Kerry Adriaensen, Wim Vanham, Guido Ogunjimi, Benson Laukens, Kris Vercauteren, Koen Meysman, Pieter |
author_sort | Postovskaya, Anna |
collection | PubMed |
description | Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) – epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. These models were then applied to longitudinal CD8+ TCR repertoires from critical and non-critical COVID-19 patients. In spite of comparable initial CoV-common TCR repertoire depth and CD8+ T-cell depletion, the temporal dynamics of SC2-unique TCRs differed depending on the disease severity. Specifically, while non-critical patients demonstrated a large and diverse SC2-unique TCR repertoire by the second week of the disease, critical patients did not. Furthermore, only non-critical patients exhibited redundancy in the CD8+ T-cell response to both groups of epitopes, SC2-unique and CoV-common. These findings indicate a valuable contribution of the SC2-unique CD8+ TCR repertoires. Therefore, a combination of specific and cross-reactive CD8+ T-cell responses may offer a stronger clinical advantage. Besides tracking the specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire, our analytical framework can be expanded to more epitopes and assist in the assessment and monitoring of CD8+ T-cell response to other infections. |
format | Online Article Text |
id | pubmed-10264683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102646832023-06-15 Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution Postovskaya, Anna Vujkovic, Alexandra de Block, Tessa van Petersen, Lida van Frankenhuijsen, Maartje Brosius, Isabel Bottieau, Emmanuel Van Dijck, Christophe Theunissen, Caroline van Ierssel, Sabrina H. Vlieghe, Erika Bartholomeus, Esther Mullan, Kerry Adriaensen, Wim Vanham, Guido Ogunjimi, Benson Laukens, Kris Vercauteren, Koen Meysman, Pieter Front Immunol Immunology Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) – epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. These models were then applied to longitudinal CD8+ TCR repertoires from critical and non-critical COVID-19 patients. In spite of comparable initial CoV-common TCR repertoire depth and CD8+ T-cell depletion, the temporal dynamics of SC2-unique TCRs differed depending on the disease severity. Specifically, while non-critical patients demonstrated a large and diverse SC2-unique TCR repertoire by the second week of the disease, critical patients did not. Furthermore, only non-critical patients exhibited redundancy in the CD8+ T-cell response to both groups of epitopes, SC2-unique and CoV-common. These findings indicate a valuable contribution of the SC2-unique CD8+ TCR repertoires. Therefore, a combination of specific and cross-reactive CD8+ T-cell responses may offer a stronger clinical advantage. Besides tracking the specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire, our analytical framework can be expanded to more epitopes and assist in the assessment and monitoring of CD8+ T-cell response to other infections. Frontiers Media S.A. 2023-05-31 /pmc/articles/PMC10264683/ /pubmed/37325653 http://dx.doi.org/10.3389/fimmu.2023.1130876 Text en Copyright © 2023 Postovskaya, Vujkovic, de Block, van Petersen, van Frankenhuijsen, Brosius, Bottieau, Van Dijck, Theunissen, van Ierssel, Vlieghe, Bartholomeus, Mullan, Adriaensen, Vanham, Ogunjimi, Laukens, Vercauteren and Meysman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Postovskaya, Anna Vujkovic, Alexandra de Block, Tessa van Petersen, Lida van Frankenhuijsen, Maartje Brosius, Isabel Bottieau, Emmanuel Van Dijck, Christophe Theunissen, Caroline van Ierssel, Sabrina H. Vlieghe, Erika Bartholomeus, Esther Mullan, Kerry Adriaensen, Wim Vanham, Guido Ogunjimi, Benson Laukens, Kris Vercauteren, Koen Meysman, Pieter Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution |
title | Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution |
title_full | Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution |
title_fullStr | Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution |
title_full_unstemmed | Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution |
title_short | Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution |
title_sort | leveraging t-cell receptor – epitope recognition models to disentangle unique and cross-reactive t-cell response to sars-cov-2 during covid-19 progression/resolution |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264683/ https://www.ncbi.nlm.nih.gov/pubmed/37325653 http://dx.doi.org/10.3389/fimmu.2023.1130876 |
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