Synapse propensity of human memory CD8 T cells confers competitive advantage over naïve counterparts

Abstract

2Memory T cells are endowed with multiple functional features that enable them to be more 3 protective than naïve T cells against infectious threats. It is not known if memory cells have a 4 higher synapse propensity, i.e. increased probability to form immature immunological 5 synapses that then provide an entry into different modes of durable interaction with antigen 6 presenting cells. Here we show that only human memory CD8 T cells have remarkably high 7 synapse propensity compared to naïve counterparts. Such a dichotomy between naïve and 8 memory cells is not observed within the human CD4 or murine CD8 T cell population. 9 Increased surface expression of LFA1 contributes to the higher synapse propensity in human 10 memory CD8 T cells. Finally, we show that higher synapse propensity in human memory 11 CD8 T cells allows them to compete out naïve CD8 T cells from getting recruited to the 12 response. This observation has implications for original antigenic sin and aging of the 13 immune system in humans. 14 15

A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

“…Gradual accumulation of arrested cells is an indication of efficient search by the T cells and induction of arrest due to TCR-pMHC interactions. The attachment profile is comparable to that of untouched cells engaging with anti-CD3 stimulatory spots 31 . (c) The number of remaining attached cells on stimulatory spots as a function of time after the first 40 minutes of imaging.…”