SARS-CoV-2 breakthrough infections recall spike-specific memory T cells established by vaccination and induce primary T cell responses against non-vaccine-encoded viral antigens. In Immunity, Juno and colleagues use fluorescently conjugated pMHCI and pMHCII multimers that present known CD8+ and CD4+ T cell viral epitopes to examine the frequency and phenotype of CD8+ and CD4+ T cells after Delta or Omicron (BA.1 and BA.2) breakthrough infection in previously vaccinated individuals. They found that spike-specific CD4+ T cells occur at day 2, peak at day 5.4, and are mostly CD45RA−CCR7+ central memory and CD45RA−CCR7− effector memory T cells. Spike-specific CD8+ T cells expanded at day 4 and peaked at day 6, with variable frequency between participants. Nucleocapsid-specific T cells had a naive phenotype and low frequency at days 2–4, and progressively acquired a CD38+CCR5+CXCR3+GzmB+CD71+ effector program. The frequency of spike-specific CD8+ T cells, but not the frequency of spike-specific CD4+ T cells, nucleocapsid-specific CD8+ T cells or neutralizing antibodies titers, positively correlated with the rate of viral clearance. Multiple vaccinations and infections resulted in 3–240-fold higher frequencies of spike-specific CD4+ and CD8+ memory T cells than pre-vaccination levels, which indicates the durability of vaccine-induced memory T cells.