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On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned
T cells recognize pathogens by their highly specific T-cell receptor (TCR), which can bind small fragments of an antigen presented on the Major Histocompatibility Complex (MHC). Antigens that are provided through vaccination cause specific T cells to respond by expanding and forming specific memory...
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/PMC10374308/ https://www.ncbi.nlm.nih.gov/pubmed/37520553 http://dx.doi.org/10.3389/fimmu.2023.1210168 |
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author | de Greef, Peter C. Lanfermeijer, Josien Hendriks, Marion Cevirgel, Alper Vos, Martijn Borghans, José A. M. van Baarle, Debbie de Boer, Rob J. |
author_facet | de Greef, Peter C. Lanfermeijer, Josien Hendriks, Marion Cevirgel, Alper Vos, Martijn Borghans, José A. M. van Baarle, Debbie de Boer, Rob J. |
author_sort | de Greef, Peter C. |
collection | PubMed |
description | T cells recognize pathogens by their highly specific T-cell receptor (TCR), which can bind small fragments of an antigen presented on the Major Histocompatibility Complex (MHC). Antigens that are provided through vaccination cause specific T cells to respond by expanding and forming specific memory to combat a future infection. Quantification of this T-cell response could improve vaccine monitoring or identify individuals with a reduced ability to respond to a vaccination. In this proof-of-concept study we use longitudinal sequencing of the TCRβ repertoire to quantify the response in the CD4+ memory T-cell pool upon pneumococcal conjugate vaccination. This comes with several challenges owing to the enormous size and diversity of the T-cell pool, the limited frequency of vaccine-specific TCRs in the total repertoire, and the variation in sample size and quality. We defined quantitative requirements to classify T-cell expansions and identified critical parameters that aid in reliable analysis of the data. In the context of pneumococcal conjugate vaccination, we were able to detect robust T-cell expansions in a minority of the donors, which suggests that the T-cell response against the conjugate in the pneumococcal vaccine is small and/or very broad. These results indicate that there is still a long way to go before TCR sequencing can be reliably used as a personal biomarker for vaccine-induced protection. Nevertheless, this study highlights the importance of having multiple samples containing sufficient T-cell numbers, which will support future studies that characterize T-cell responses using longitudinal TCR sequencing. |
format | Online Article Text |
id | pubmed-10374308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103743082023-07-28 On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned de Greef, Peter C. Lanfermeijer, Josien Hendriks, Marion Cevirgel, Alper Vos, Martijn Borghans, José A. M. van Baarle, Debbie de Boer, Rob J. Front Immunol Immunology T cells recognize pathogens by their highly specific T-cell receptor (TCR), which can bind small fragments of an antigen presented on the Major Histocompatibility Complex (MHC). Antigens that are provided through vaccination cause specific T cells to respond by expanding and forming specific memory to combat a future infection. Quantification of this T-cell response could improve vaccine monitoring or identify individuals with a reduced ability to respond to a vaccination. In this proof-of-concept study we use longitudinal sequencing of the TCRβ repertoire to quantify the response in the CD4+ memory T-cell pool upon pneumococcal conjugate vaccination. This comes with several challenges owing to the enormous size and diversity of the T-cell pool, the limited frequency of vaccine-specific TCRs in the total repertoire, and the variation in sample size and quality. We defined quantitative requirements to classify T-cell expansions and identified critical parameters that aid in reliable analysis of the data. In the context of pneumococcal conjugate vaccination, we were able to detect robust T-cell expansions in a minority of the donors, which suggests that the T-cell response against the conjugate in the pneumococcal vaccine is small and/or very broad. These results indicate that there is still a long way to go before TCR sequencing can be reliably used as a personal biomarker for vaccine-induced protection. Nevertheless, this study highlights the importance of having multiple samples containing sufficient T-cell numbers, which will support future studies that characterize T-cell responses using longitudinal TCR sequencing. Frontiers Media S.A. 2023-07-13 /pmc/articles/PMC10374308/ /pubmed/37520553 http://dx.doi.org/10.3389/fimmu.2023.1210168 Text en Copyright © 2023 de Greef, Lanfermeijer, Hendriks, Cevirgel, Vos, Borghans, van Baarle and de Boer 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 de Greef, Peter C. Lanfermeijer, Josien Hendriks, Marion Cevirgel, Alper Vos, Martijn Borghans, José A. M. van Baarle, Debbie de Boer, Rob J. On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned |
title | On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned |
title_full | On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned |
title_fullStr | On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned |
title_full_unstemmed | On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned |
title_short | On the feasibility of using TCR sequencing to follow a vaccination response – lessons learned |
title_sort | on the feasibility of using tcr sequencing to follow a vaccination response – lessons learned |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374308/ https://www.ncbi.nlm.nih.gov/pubmed/37520553 http://dx.doi.org/10.3389/fimmu.2023.1210168 |
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