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Open Access Green as soon as Postprint is submitted to ZB.
Vaccination-induced T cell responses maintain polyclonality with high antigen receptor avidity.
Sci. Immunol. 10:eadu6730 (2025)
Clonal expansion is a hallmark of adaptive immunity and has been challenging to investigate in humans in a standardized manner compared with animal models. We studied a cohort of 29 healthy individuals who received three mRNA vaccinations against SARS-CoV-2 before a breakthrough infection. We characterized the magnitude, phenotype, and clonal composition of CD8 T cell responses against 16 epitope specificities by ELISpot; flow cytometry; and single-cell RNA, protein, and T cell receptor (TCR) sequencing. One hundred six TCRs from five epitope-specific repertoires were reexpressed and tested for peptide sensitivity. Whereas vaccination-recruited T cell repertoires were enriched for high-avidity TCRs, differential clonal expansion was not linked to fine avidity differences. Instead, maintenance of polyclonality ensured robustness in counteracting viral mutational escape through altered epitopes. Deciphering the functionality of human antigen-specific T cell repertoires instructs our understanding of human T cell biology and may guide the development of vaccines and other immunotherapies.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Precursor Frequency; Selection; Differentiation; Repertoire; Memory; Sars-cov-2; Evolution; Vaccines; Fate; Hiv
Language
english
Publication Year
2025
HGF-reported in Year
2025
ISSN (print) / ISBN
2470-9468
e-ISSN
2470-9468
Journal
Science immunology
Quellenangaben
Volume: 10,
Issue: 112,
Article Number: eadu6730
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
Washington, DC
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503800-001
Grants
European Union
Else Kroner-Fresenius-Stiftung
German Research Foundation (DFG) through the research training group RTG 2504
Yellow4FLAVI project - European Union, under the Horizon Europe Programme
Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nurnberg
BMBF
Helmholtz Association under the joint research school "Munich School for Data Science-MUDS"
Joachim Herz Stiftung
Hightech Agenda Bavaria
German Federal Ministry of Education and Research (BMBF)
Else Kroner-Fresenius-Stiftung
German Research Foundation (DFG) through the research training group RTG 2504
Yellow4FLAVI project - European Union, under the Horizon Europe Programme
Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nurnberg
BMBF
Helmholtz Association under the joint research school "Munich School for Data Science-MUDS"
Joachim Herz Stiftung
Hightech Agenda Bavaria
German Federal Ministry of Education and Research (BMBF)
WOS ID
001586207400002
Scopus ID
105017654806
PubMed ID
41042909
Erfassungsdatum
2025-11-06