Distal inhibition of stimulatory immune signalling by LAIR-1

Inhibitory immune receptors play a key role in balancing the immune response. Within an immunological synapse, inhibitory receptors recruit phosphatases that can deactivate stimulatory immune receptors within a range of ~20 nm. However, it is unknown how an immune response can be suppressed when inhibitory and stimulatory receptors are separated over a longer distance.

In this project, I will study distal immune inhibition using the prototype inhibitory receptor LAIR-1. We hypothesize that LAIR-1-mediated recruitment of CSK to the plasma membrane drives distal inhibition of stimulatory signalling by depleting the pool of active Src family kinases (SFKs) required for stimulatory receptor activation. Using TIRF microscopy, I will study the kinetics of signalling proteins and their interactions with LAIR-1. Furthermore, I will measure the activation status of SFKs through a biosensor with single-molecule resolution.

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Tom Aarts