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.