Temporal dynamics of antigen-specific T cell expansion in primary SARS-CoV-2 infection
Abstract Quantifying T cell response during primary infection in humans is crucial for understanding adaptive immunity. Leveraging a controlled human challenge to SARS-CoV-2, we characterized antigen-specific T cell response within and across individuals. Notably, individual clones reached similar maximum frequencies despite differences in the timing of their peak expansion. Mathematical modeling showed that this observation is consistent with precursor frequency, but not TCR signal strength, as the source of inter-clonal variability. Single-cell profiling revealed distinct temporal programs for CD4 + and CD8 + T cells, with CD4 + cells expanding earlier but contracting to a lower frequency. Clones with similar receptors, likely recognizing the same antigen, expanded at similar times. Together, these findings highlight how clone-intrinsic properties such as precursor frequency and lineage shape T cell clonal kinetics. These insights provide a quantitative framework for understanding T cell response in humans, with implications for vaccine design.
Authors
- Ben Killingley (ORCID: https://orcid.org/0000-0003-0714-2426)
- Suzanne Byrne (ORCID: https://orcid.org/0009-0009-2779-7922)
- Alex Mann (ORCID: https://orcid.org/0000-0002-3744-4604)
- Mahdad Noursadeghi (ORCID: https://orcid.org/0000-0002-4774-0853)
- Christopher Chiu (ORCID: https://orcid.org/0000-0003-0914-920X)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- Curtis G. Callan (ORCID: https://orcid.org/0000-0001-9937-6160)
- Andrew G. T. Pyo (ORCID: https://orcid.org/0009-0009-3045-4832)
- Joshua Rosenheim (ORCID: https://orcid.org/0000-0003-0171-2053)
- Rik G.H. Lindeboom (ORCID: https://orcid.org/0000-0002-3660-504X)
- Marko Nikolić (ORCID: https://orcid.org/0000-0001-6304-6848)
- Benny Chain (ORCID: https://orcid.org/0000-0002-7417-3970)
- Helen R. Wagstaffe (ORCID: https://orcid.org/0000-0002-4462-7484)
- Lucy C. K. Bell (ORCID: https://orcid.org/0000-0002-1762-7294)
- Clare E Thakker (ORCID: https://orcid.org/0000-0002-1907-3176)
- Alison Boyers
- Gayathri Nageswaran (ORCID: https://orcid.org/0009-0005-7449-0924)
- Ned S. Wingreen (ORCID: https://orcid.org/0000-0001-7384-2821)
- Mariya Kalinova
- Andrew P. Catchpole (ORCID: https://orcid.org/0000-0003-1795-1008)
Institutions
- Princeton University (US)
- University of Cambridge (GB)
- The Netherlands Cancer Institute (NL)
- hVIVO (United Kingdom) (GB)
- University College London (GB)
- Imperial College London (GB)
- Stanford University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-11-06
- DOI
- https://doi.org/10.1126/sciadv.aec4195
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 8.10
Funders
- Princeton University
- Wellcome Trust
- Chan Zuckerberg Initiative
- Royal Free London NHS Foundation Trust
- Rosetrees Trust
- Natural Sciences and Engineering Research Council of Canada
- NIHR Imperial Biomedical Research Centre