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

Kocher K, Drost F, Tesfaye AM, Moosmann C, Schülein C, Grotz M, D'Ippolito E, Graw F, Spriewald B, Busch DH, Bogdan C, Tenbusch M, Schubert B, Schober K (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Science immunology American Association for the Advancement of Science

Book Volume: 10

Pages Range: eadu6730-

Journal Issue: 112

DOI: 10.1126/sciimmunol.adu6730

Abstract

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.

Authors with CRIS profile

Katharina Kocher Lehrstuhl für Mikrobiologie und Infektionsimmunologie Carolin Moosmann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Christine Schülein Lehrstuhl für Biochemie und Molekulare Medizin Myriam Grotz Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Frederik Graw Professur für Modellierung von Immunprozessen Bernd Spriewald Department of Medicine 5 – Haematology and Oncology Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Kocher, K., Drost, F., Tesfaye, A.M., Moosmann, C., Schülein, C., Grotz, M.,... Schober, K. (2025). Vaccination-induced T cell responses maintain polyclonality with high antigen receptor avidity. Science immunology, 10(112), eadu6730-. https://doi.org/10.1126/sciimmunol.adu6730

MLA:

Kocher, Katharina, et al. "Vaccination-induced T cell responses maintain polyclonality with high antigen receptor avidity." Science immunology 10.112 (2025): eadu6730-.

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