Vaccination reshapes the virus-specific T cell repertoire in unexposed adults
Name
nihms-1697836.pdf
Description
Accepted version
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2.02 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Pan, Yi-Gen
Aiamkitsumrit, Benjamas
Bartolo, Laurent
Wang, Yifeng
Lavery, Criswell
Marc, Adam
Holec, Patrick V
Rappazzo, C Garrett
Eilola, Theresa
Gimotty, Phyllis A
Date Issued
2021
Journal
Immunity
Publisher
Elsevier BV
Citation
Pan, Yi-Gen, Aiamkitsumrit, Benjamas, Bartolo, Laurent, Wang, Yifeng, Lavery, Criswell et al. 2021. "Vaccination reshapes the virus-specific T cell repertoire in unexposed adults." Immunity, 54 (6).
Version
Author's final manuscript
Abstract
We examined how baseline CD4+ T cell repertoire and precursor states impact responses to pathogen infection in humans using primary immunization with yellow fever virus (YFV) vaccine. YFV-specific T cells in unexposed individuals were identified by peptide-MHC tetramer staining and tracked pre- and post-vaccination by tetramers and TCR sequencing. A substantial number of YFV-reactive T cells expressed memory phenotype markers and contained expanded clones in the absence of exposure to YFV. After vaccination, pre-existing YFV-specific T cell populations with low clonal diversity underwent limited expansion, but rare populations with a reservoir of unexpanded TCRs generated robust responses. These altered dynamics reorganized the immunodominance hierarchy and resulted in an overall increase in higher avidity T cells. Thus, instead of further increasing the representation of dominant clones, YFV vaccination recruits rare and more responsive T cells. Our findings illustrate the impact of vaccines in prioritizing T cell responses and reveal repertoire reorganization as a key component of effective vaccination.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.IMMUNI.2021.04.023
