Antigen-induced Erk1/2 activation regulates Ets-1-mediated sensitization of CD8+ T cells for IL-12 responses.

The presence of IL-12 during antigen stimulation instructs naive CD8+ T cells for long-term effector responses, but their mechanisms of collaboration are not understood completely. Herein, we report that CD8+ T cells (OT-I T cells) stimulated with antigen for a longer duration show enhanced sensitization to IL-12 as a result of Erk1/2-dependent, increased Ets-1 phosphorylation and subsequent increases in IL-12Rbeta2 expression. Correspondingly, naive OT-I T cells stimulated by antigen for a longer duration in the presence of IL-12, irrespective of frequency of APCs, show robust effector maturation and mount long-term antigen-recall responses upon adoptive transfer. These results identify the role of antigen strength-dependent Erk1/2 activation for Ets-1-mediated collaboration with IL-12 in CD8+ T cells.