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1. Introduction
2. Acknowledgements
3. T cell development and function
4. T cell activation
5. From nave to activated cytotoxic T cells (1)
6. Immune activation regulates different processes
7. From nave to activated cytotoxic T cells (2)
8. Primary T cells express approx. 24,566 genes
9. The key question
10. The immunological synapse
11. T cell activation: lots of receptors
12. Our focus is the serine kinase networks
13. The human kinome
14. How complex is the T cell phosphoproteome?
15. Identification of serine threonine phosphorylations
16. Kinases predicted to be active in CTL (1)
17. Functions of the CTL phosphoproteins
18. Serine/ threonine kinases in T cell biology
19. Kinases predicted to be active in CTL (2)
20. PKB signal transduction
21. Tools to probe PI3K/PDK1/PKB's role in CTL
22. Inhibitors prevent phosphorylation of PKB in CTL
23. AktI 1/2 blocks phosphorylation and activity of PKB
24. Deletion of PDK1 blocks PKB/Akt activation
25. What is the role of PKB/Akt in CTL?
26. CTL express approximately 9405 genes
27. Inhibition of PKB and decrease in cytolytic effectors
28. Inhibition of PKB and downregulation of perforin
29. PKB determines repertoire of cytokine receptors
30. PKB increases expression of CD62L and CCR7
31. What are CCR7 and CD62L?
32. Primary naive T cells
33. CD62L and CCR7 direct lymphocyte transmigration
34. CTL lose expression of CCR7 and CD62L
35. CD62L and CCR7 in naive/ memory and CD8 T cells
36. CD62L and CCR7 mRNA expression
37. PKB inhibition restores CD62L and CCR7
38. Can PKB inhibition reprogram T cell trafficking?
39. In vivo homing experiments
40. CTL treated with PKB inhibitor regain homing ability
41. Will PIP3 & PKB activation switch off CCR7,CD62L?
42. How to get increased PIP3 and PKB activation
43. PTEN deletions/downregulation occur in tumours
44. Producing CTL that lack both PTEN and PDK1
45. PTEN deletion stimulates PKB activity via PDK1
46. PTEN deletion de-regulates adhesion, chemokines
47. PTEN-null T cells don't home to lymphoid organs
48. PKB required to switch off CD62L & CCR7
49. PKB phosphorylates Foxo1 and Foxo3A
50. Does non phosphorylatable Foxo restore CD62L?
51. Phosphorylated Foxo restores CD62L expression
52. How does Foxo control CD62L & CCR7 expression
53. PKB activity down-regulates KLF2 mRNA (1)
54. PKB activity down-regulates KLF2 mRNA (2)
55. Inhibition of PI3K or PKB restores KLF2 expression
56. Re-expression of KLF2 in CTL upregulates CD62L
57. PKB cascade and KLF2
58. PKB controls T cell trafficking via Foxo
59. Summary of nave vs. cytotoxic cells
60. Serine kinase are important in T cells
61. Many more genes to work on

Topics Covered

• T cell development and function
• T cell activation
• Serine kinase networks
• T cell phosphoproteome
• Kinases active in CTL
• Functions of the CTL phosphoproteins
• PKB signal transduction
• PKB/Akt role in CTL
• Inhibition of PKB
• CCR7 and CD62L
• Homing ability in CTL
• PIP3 & PKB activation
• PTEN deletion/down-regulation effect
• PKB phosphorylates Foxo1 and Foxo3A
• Foxo and CD62L & CCR7 expression
• PKB cascade and KLF2
• PKB controls T cell trafficking via Foxo

Links

Series:

• Protein Phosphorylation

Categories:

• Biochemistry
• Cell Biology
• Immunology

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Publication History

• Published on August 15, 2011

Financial Disclosures

• Prof. Doreen Cantrell has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.