The study by Mempel, Henrickson, and von Andrian investigates the priming of naive T cells by dendritic cells (DCs) in lymph nodes (LNs). Using two-photon microscopy, they observed that T-cell priming occurs in three distinct phases: 1. **First Phase (0-8 hours)**: T cells undergo multiple short encounters with DCs, decrease their motility, and upregulate activation markers. 2. **Second Phase (8-24 hours)**: T cells form long-lasting stable conjugates with DCs, begin to secrete interleukin-2 and interferon-γ, and exhibit a transition to a more stable contact state. 3. **Third Phase (24-48 hours)**: T cells resume rapid migration and short DC contacts, and start to proliferate. The researchers found that the duration and stability of T-cell-DC interactions are influenced by the presence of antigen and the dwell time of T cells in the LN. The formation of mature synapse-like contacts during the second phase is crucial for T-cell activation, while the brief interactions in the first phase are sufficient for early activation markers. The study provides a comprehensive understanding of the sequential stages of T-cell priming by DCs in a physiological setting.The study by Mempel, Henrickson, and von Andrian investigates the priming of naive T cells by dendritic cells (DCs) in lymph nodes (LNs). Using two-photon microscopy, they observed that T-cell priming occurs in three distinct phases: 1. **First Phase (0-8 hours)**: T cells undergo multiple short encounters with DCs, decrease their motility, and upregulate activation markers. 2. **Second Phase (8-24 hours)**: T cells form long-lasting stable conjugates with DCs, begin to secrete interleukin-2 and interferon-γ, and exhibit a transition to a more stable contact state. 3. **Third Phase (24-48 hours)**: T cells resume rapid migration and short DC contacts, and start to proliferate. The researchers found that the duration and stability of T-cell-DC interactions are influenced by the presence of antigen and the dwell time of T cells in the LN. The formation of mature synapse-like contacts during the second phase is crucial for T-cell activation, while the brief interactions in the first phase are sufficient for early activation markers. The study provides a comprehensive understanding of the sequential stages of T-cell priming by DCs in a physiological setting.