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SUMMARY:Hedgehog signalling in Cytotoxic T cell function - Maike de la Roc
 he\, Cambridge Institute for Medical Research
DTSTART:20150107T161500Z
DTEND:20150107T171500Z
UID:TALK56318@talks.cam.ac.uk
CONTACT:Fiona Roby
DESCRIPTION:Cytotoxic T Lymphocytes (CTL) are an important part of the ada
 ptive immune system and can kill virally infected and tumorigenic cells. T
 he centrosome plays a critical role in CTL function\, docking at the plasm
 a membrane and directing cytotoxic granules for secretion at the immunolog
 ical synapse (IS).  Centrosome docking at the plasma membrane is very unus
 ual but also occurs during cilia formation.  The primary cilium\, formed b
 y virtually all cells\, is essential for vertebrate Hedgehog (Hh) signalli
 ng. Lymphocytes do not form primary cilia\, but here we found that Hh sign
 alling played an important role in CTL killing. T cell receptor (TCR) acti
 vation\, which pre-arms CTL with cytotoxic granules\, also initiated Hh si
 gnalling. Hh pathway activation occurred intracellularly and triggered Rac
 1 synthesis.  These events “pre-armed” CTL for the actin remodelling r
 equired for centrosome polarisation and granule release.  Inhibition of Hh
  signalling either genetically or with small molecule inhibitors led to di
 minished CTL killing. In contrast\, CTL from patients with Gorlin syndrome
 \, which have hyperactive Hh signalling due to a mutation of the negative 
 pathway regulator PTCH1\, have greatly increased killing capacity compared
  to CTL from healthy donor controls.
LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine
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