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Kocher, K.* ; Drost, F. ; Tesfaye, A.M.* ; Moosmann, C.* ; Schülein, C.* ; Grotz, M.* ; D'Ippolito, E.* ; Graw, F.* ; Spriewald, B.* ; Busch, D.H.* ; Bogdan, C.* ; Tenbusch, M.* ; Schubert, B. ; Schober, K.*

Vaccination-induced T cell responses maintain polyclonality with high antigen receptor avidity.

Sci. Immunol. 10:eadu6730 (2025)

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Open Access Green as soon as Postprint is submitted to ZB.

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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

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)

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)