The responsiveness of CD8+ T cells is "imprinted" during the priming phase through PD-1 acquisition. The upper panel depicts the general methodology: mice were immunized by various regimens and specific T cells were restimulated ex vivo with HLA-A*0201-binding human Melan A 26-35 native peptide (EAAGIGILTV), in the presence of PD-1 blocking antibodies or control immunoglobulin. Ex vivo T cell proliferation was measured using a standard CFSE staining assay. The bottom panel depicts a summary of the results comparing the essential groups: T cells from Melan A plasmid versus Melan A 26-35 analogue peptide (ELAGIGILTV) immunized mice. While the epitope-specific T cells from DNA vaccinated mice had low PD-1 expression and high proliferative potential persistently, the T cells from peptide immunized mice had high PD-1 expression and low proliferative potential; however, their proliferation could be easily restored through blocking PD-1/PD-1L interaction, speaking to the critical role of PD-1 in determining the fate of CD8+ T cells post-priming (summary of results in refs.  and ).