Temporal dynamics of antigen-specific T cell expansion in primary SARS-CoV-2 infection.

Antigen-specific T cell clones during primary SARS-CoV-2 infection reached similar maximum frequencies despite differences in when their peak expansion occurred.

• Why it matters: Understanding how human T cell clones expand over time during primary infection is key to explaining adaptive immunity and improving how vaccines are designed.
• What they did: Using a controlled human challenge, the study quantified antigen-specific T cell responses across and within individuals, combined with coarse-grained mathematical modeling and single-cell profiling to track CD4+ and CD8+ temporal programs.
• The result: Modeling suggested variability in precursor frequency between clones may explain the timing–maximum-frequency relationship, while single-cell data showed CD4+ expanding earlier but contracting to a lower frequency, and similarly receptor-defined clones expanding at similar times.

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