MEK-mediated phosphorylation of ERK and the repertoire of antigen specificities differ according to the stage of memory T-cell differentiation. MEK-mediated phosphorylation of ERK decreases progressively across stages of memory differentiation after activation of T_N, T_CM, T_EM, and T_EMRA cells that express CD45RA (T_EMRA). Alloantigens are recognized more effectively by the T_N cell population than by memory populations, while protection against pathogens is mediated more effectively by memory populations than by the T_N cell population. Professional illustration by Paulette Dennis.