Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions

• Stable DC-CD8+ T cell contacts are not required for effector T cell differentiation
• Memory differentiation of CD8+ T cells is correlated with stable DC-T cell contacts
• Low- and high-dose antigen initiate distinct transcriptional programs in T cells
• CD8+ T cells make a memory fate decision within 24 hr after antigen encounter

SummaryT cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8+ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics.

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