SKG

Question 1

SKG signaling defects

Answer 1

Decreased pZap70, pZeta pLat and PLCg.
No association with zeta (IP zap70, blot zeta)
Decreased ca++ responses (Letters to nature, 2003, sakaguchi)

Question 2

SKG proliferative defects

Answer 2

SKG CD4+ cells respond to 1 uM ova peptide in the same way that B/C DO cells responde to 0.1 uM ova peptide.
(Letters to nature, 2003, sakaguchi)
Oddly the pMA/iono proliferation is also decreased suggesting that they are just inherently less able to respond?

Question 3

SKG Thymocytes and Apoptosis

Answer 3

SKG thymocytes undergo apoptosis in response to dexamethazone treatment but are resistant to TCR induced apoptosis (Either CD3 or ova p323-339) (ova p324-334 is the -ve control for apoptosis induction) (Letters to nature, 2003, sakaguchi)

Question 4

SKG Signaling defects - Mapk

Answer 4

ERK1/2 are phosphorylated really strongly at 1 and 2 min, and starts to wane by 5 but is still detectable out to 30 min in WT thymocytes stimulated with anti CD3 (only). pErk is only detectable at 1 and 2 min in SKG.

Question 5

SKG and T cell development

Answer 5

SKG thymus contains a higher number of TCR low (Immature) thymocytes. Periperal T cell numbers are reduced for both CD4 and CD8. increased B cells.
(Letters to nature, 2003, sakaguchi)

Question 6

Things that are not significantly affected by SKG

Answer 6

Total Thymocyte #, Total Splenocyte #, number or function of NK cells, representation of Va or Vb families
(Letters to nature, 2003, sakaguchi)

Question 7

DO.SKG - T cell selection

Answer 7

of CD4+ thymocytes is 20% of wildtype
only 30% express the DO TCR (and about 50% in the het) Compared to 80% in WT DO mice. (KJ1-26 clonotypic antibody). Vb8 expression is comparable in periphery suggesting that endogenous aChains are expressed.
(Letters to nature, 2003, sakaguchi)
high incidence of arthritis in both males and females

Question 8

HY TCR

Answer 8

Selection doesn’t occur in female SKG mice but is occurs in males at levels that are comparable to selection in WT females
(these mice were on H2b background somehow)
high incidence of arthritis in both males and females