LAT

Question 1

LatY136F mice

Answer 1

Severe but incomplete block in conventional CD4 and CD8 cells
Within 2 weeks - massive lymphoproliferation and TH2 differention (in the absence of immunization)
Epic germinal centers and hypergammaglobulinemia - death by 4-6 weeks

Question 2

positive Lat Plugins

Answer 2

pY 136, 175, 195, 235 (mouse)

Question 3

LAT and PLCg

Answer 3

CA++: pLat recruits SLP76 (Via Grap2) which is phosphorylated by Zap70. SLP76 recruits ITK, which phosphorylates PLCg1 which then makes IP3 and DAG (ie calcium)
DAG recruits Ras Grp, which activates Ras and therefore ERK1/2

Question 4

Tregs in LatY136F mice

Answer 4

Don’t function properly, but this is not the cause of autoimmunity

Question 5

TCR levels in LatY136F mice

Answer 5

Low, and TCR is unnecessary - the T cells can proliferate and activate B cells in the absence of MHCII (CD28 i guess is responsible for the fact that they don’t need TCR to be a T cell)

Question 6

Lat Nanoclusters

Answer 6

Multiple Proteins compete for binding to lat pY

Up to 3 grb2 molecules can interact with LAT and SOS can bind Grb2 at 2 sites, so this can pull together the different isoforms of complexes that are bound to lat.