Question

1a. List the following in the correct order in which they occur during T lymphocyte activation: Ca++ accumulation in the cytoplasm, binding of TCR to peptide + MHC, phospholipase C, CD3 phosphorylation, transcription factor necrosis, tyrosine kinase lck, DAG and IP3 synthesis, ZAP kinase.

b. Describe specifically how NFkB, NFAT, are activated and what is their function?

Answer 1

A.

1. Binding of TCR to peptide + MHC
2. tyrosine kinase lck
3. CD3 phosphorylation
4. ZAP kinase.
5. phospholipase C
6. DAG and IP3 synthesis
7. Ca++ accumulation in the cytoplasm
8. transcription factor necrosis

B. Antigen recognition by the T-cell receptor and its co-receptors leads to phosphorylation of ITAMs by Src-family kinases.
Then ZAP 70 activated is recruited by the SH2 domain.
It activates the PLC-gamma
PLC cleaves PIP2 to IP3 and DAG
IP3 - opens calcium channels in the ER to release Ca2+
DAG - recruits PKC and Ras
Ca2+ activates - the transcription factor NFAT.
PKC (protein kinase C) activates - the transcription factors NF?-B.

TFs NFAT, NF?-B - activates transcription leading to cell proliferation and differentiation.