Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: de Greef, Peter C., Lanfermeijer, Josien, Hendriks, Marion, Cevirgel, Alper, Vos, Martijn, Borghans, José A. M., van Baarle, Debbie, de Boer, Rob J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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
_version_ 1785078745956089856
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
work_keys_str_mv AT degreefpeterc onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT lanfermeijerjosien onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT hendriksmarion onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT cevirgelalper onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT vosmartijn onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT borghansjoseam onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT vanbaarledebbie onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned
AT deboerrobj onthefeasibilityofusingtcrsequencingtofollowavaccinationresponselessonslearned