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Memory T cells are endowed with multiple functional features that enable them to be more protective than naïve T cells against infectious threats. It is not known if memory cells have a higher synapse propensity, i.e. increased probability to form immature immunological synapses that then provide an entry into different modes of durable interaction with antigen presenting cells. Here we show that only human memory CD8 T cells have remarkably high synapse propensity compared to naïve counterparts. Such a dichotomy between naïve and memory cells is not observed within the human CD4 or murine CD8 T cell population. Increased surface expression of LFA1 contributes to the higher synapse propensity in human memory CD8 T cells. Finally, we show that higher synapse propensity in human memory CD8 T cells allows them to compete out naïve CD8 T cells from getting recruited to the response. This observation has implications for original antigenic sin and aging of the immune system in humans.

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