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In a human SARS-CoV-2 challenge, T cell clones peaked at similar frequencies but at different times

A controlled human SARS-CoV-2 challenge showed that CD4+ and CD8+ T cells follow distinct time courses, and that precursor frequency explains differences between clones.

In a human SARS-CoV-2 challenge, T cell clones peaked at similar frequencies but at different times
Photo: Lubos Polerecky, Takako Masuda, Meri Eichner, Sophie Rabouille, Marie Vancová, Michiel V. , Wikimedia Commons, CC BY-SA 4.0 · License: CC BY-SA 4.0

Researchers characterized antigen-specific T cell responses within and across individuals during primary SARS-CoV-2 infection, using a controlled human challenge, according to a paper in Science Advances. science.orgScience Advancesscience.orgOpen source ↗ Individual T cell clones reached similar maximum frequencies, although the timing of their peak expansion differed.

Mathematical modeling, according to the authors, showed this is consistent with precursor frequency, rather than TCR signal strength, as the source of variability between clones. Single-cell profiling revealed distinct temporal programs for CD4+ and CD8+ T cells: CD4+ cells expanded earlier but contracted to a lower frequency.

Clones with similar receptors, likely recognizing the same antigen, expanded at similar times. The authors conclude that clone-intrinsic properties, such as precursor frequency and lineage, shape T cell clonal kinetics. They describe the results as a quantitative framework for understanding T cell response in humans, with implications for vaccine design.

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