Transcriptional profiles reveal a stepwise developmental program of memory CD8+ T cell differentiation

Highlights • We perform whole transcriptome analysis of distinct CD8+ T-cell memory populations arising endogenously following immunization with clinical and pre-clinical vaccines regimens. • We find that transcriptional proximity relationships between endogenous TN , TCM , TEM and TEFF place memory cells at an intermediate state of differentiation between TN and TEFF. • We compare transcriptional differences between TN , TCM , TEM and TEFF cells with known changes when CD8+ T cells undergo repeated antigen stimulation. • We find that at a single time-point following vaccination, cells can be found with the transcriptional imprint of distinct exposures to antigen. • Our analysis favors the progressive differentiation model whereby cumulative antigen stimulation drives differentiation specifically from TN > TCM > TEM > TEFF.