Repeated exposure to a conserved antigen drives dynamic clonal and epitope succession

Repeated COVID-19 mRNA vaccination in 38 healthy donors drives clonal succession in anti-spike CD8+ T cell memory, shifting from low-avidity clones to high-avidity clones.

• Why it matters: Epitope-level dynamics of T cell memory after vaccination are hard to map because expanded clonotypes are difficult to connect to their cognate epitopes without paired TCR information.
• What they did: Using TIRTL-seq, the study tracked paired TCRαβ from CD8+ lineages across serial samples after multiple vaccine rounds, assigning epitope specificity to 1,109 clonotypes.
• The result: The method identified 15 SARS-CoV-2 spike targets, revealed multiple previously undescribed responses, and experimentally confirmed putative specificities, enabling repertoire-based monitoring of antigen-specific immunity.

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