psycler at netcom.com
Fri May 26 00:00:31 EST 1995
Christopher J. Savoie (savoie at bioreg.kyushu-u.ac.jp) wrote:
: OK....but what are those pathways that follow...not so briefly.
: My question was perhaps
: oversimplistic to the point that you defined the major
: ligand as MHC class II and stop at
: that. Please define "signal transduction pathways". For
: example, is there interaction with
: other CD4 co-ligands (intra- or extra- cellular)
: which modulate the response to a ClassII
: MHC/peptide complex, depending on the nature of the peptide
: in the complex (self, viral,
: oncogenic, etc.)...or is CD4 just a "clamp" to hold
: the MHCII/peptide to the TCR?
: The CD4 can't be upstream of a lytic or
: cytotoxic pathway directly if it's also on APCs, can
: So, again... *specifically* what does it do?
Okay, signal transduction is not my area of expertise but I can offer
a bit of additional information. There is a tyrosine kinase, p56lck, binds
to the cytoplasmic portion of the CD4 receptor resulting in tyrosine
phosphorylation of the TCR zeta chain(s) (?).
At the same time, the TCR cytoplasmic region binds
another tyrosine kinase molecule, I think called p59fyn which also results
in tyrosine phosphorylation. Phospholipase C becomes activated leading to
hydrolysis of PIP2 into DAG (?), which then activates PKC, and IP3 in
turns raises the intracellular Ca+. In the end, the transcription of the
IL2 gene is able to take place.
Since this is not so fresh in my mind, I do stand to be corrected. Any
signal transductionists care to take a shot?
I have read that if the CD4 molecule is ligated in the absense of
antigen presentation, subsequent occupancy of the TCR will induce
apoptosis of the T cell. Human and rat T cells do express MHC class II
and have been reported to present antigen as an APC. These cells
will also express CD4 or CD8, hence an APC expressing CD4.
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