tetano
Editor, Senior Moderator
Sci Adv
. 2026 Nov 6;12(45):eaec4195.
doi: 10.1126/sciadv.aec4195. Epub 2026 Nov 6.
Andrew G T Pyo 1 2 , Adlina Chan 3 , Joshua Rosenheim 3 , Clare Thakker 3 , Lucy Bell 3 , Gayathri Nageswaran 3 , Suzanne Byrne 3 , Ben Killingley 4 , David Scobie 3 , Mariya Kalinova 5 , Alison Boyers 5 , Andrew Catchpole 5 , Alex Mann 5 , Rik G H Lindeboom 6 7 , Marko Z Nikolic 8 , Sarah A Teichmann 9 10 11 , Helen Wagstaffe 12 , Mahdad Noursadeghi 3 , Christopher Chiu 12 , Curtis G Callan Jr 1 13 , Andreas Tiffeau-Mayer 3 14 , Ned S Wingreen 15 16 , Benny Chain 3 17
Affiliations Expand
Quantifying T cell response during primary infection in humans is crucial for understanding adaptive immunity. Leveraging a controlled human challenge to severe acute respiratory syndrome coronavirus 2, we characterized antigen-specific T cell responses within and across individuals. Notably, individual clones reached similar maximum frequencies despite differences in the timing of their peak expansion. Mathematical modeling within a coarse-grained framework suggested that variability in precursor frequency between different T cell clones could be one mechanism to explain this relationship. 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 CD4/CD8 subset status shape T cell clonal kinetics. These insights provide a quantitative framework for understanding T cell response in humans, with implications for vaccine design.
. 2026 Nov 6;12(45):eaec4195.
doi: 10.1126/sciadv.aec4195. Epub 2026 Nov 6.
Temporal dynamics of antigen-specific T cell expansion in primary SARS-CoV-2 infection
Andrew G T Pyo 1 2 , Adlina Chan 3 , Joshua Rosenheim 3 , Clare Thakker 3 , Lucy Bell 3 , Gayathri Nageswaran 3 , Suzanne Byrne 3 , Ben Killingley 4 , David Scobie 3 , Mariya Kalinova 5 , Alison Boyers 5 , Andrew Catchpole 5 , Alex Mann 5 , Rik G H Lindeboom 6 7 , Marko Z Nikolic 8 , Sarah A Teichmann 9 10 11 , Helen Wagstaffe 12 , Mahdad Noursadeghi 3 , Christopher Chiu 12 , Curtis G Callan Jr 1 13 , Andreas Tiffeau-Mayer 3 14 , Ned S Wingreen 15 16 , Benny Chain 3 17
Affiliations Expand
- PMID: 42993837
- PMCID: PMC13742180
- DOI: 10.1126/sciadv.aec4195
Abstract
Quantifying T cell response during primary infection in humans is crucial for understanding adaptive immunity. Leveraging a controlled human challenge to severe acute respiratory syndrome coronavirus 2, we characterized antigen-specific T cell responses within and across individuals. Notably, individual clones reached similar maximum frequencies despite differences in the timing of their peak expansion. Mathematical modeling within a coarse-grained framework suggested that variability in precursor frequency between different T cell clones could be one mechanism to explain this relationship. 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 CD4/CD8 subset status shape T cell clonal kinetics. These insights provide a quantitative framework for understanding T cell response in humans, with implications for vaccine design.