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- Title
On the feasibility of using TCR sequencing to follow a vaccination response - lessons learned.
- Authors
de Greef, Peter C.; Lanfermeijer, Josien; Hendriks, Marion; Cevirgel, Alper; Vos, Martijn; Borghans, José A. M.; van Baarle, Debbie; de Boer, Rob J.
- Abstract
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 TCRb 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 Tcell 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.
- Subjects
MAJOR histocompatibility complex; VACCINATION; PNEUMOCOCCAL vaccines; IMMUNOLOGIC memory; T cells
- Publication
Frontiers in Immunology, 2023, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1210168