Transgenic T-cell receptor mice

Tom Thatcher ttha at uhura.cc.rochester.edu
Tue Dec 3 09:18:16 EST 1996

In article <32A41F86.5AAB at gwdg.de>, Volker Blaschke  <vblasch at gwdg.de> wrote:
>Dear fellow netters,
>I wonder if someone could answer this question that came to me AFTER 
>hearing a talk on peripheral tolerance:
>What kind of T-cell receptor to T-cell receptor transgenic mice express 
>on their T-cells? I figured the single T-cell should express both 
>receptors, the indigenous and the transgenic, but I wonder if there is a 
>kind of bilateral exclusion so that only one kind of receptor is 
>expressed and therefore there would be a subpopulation of T-cells 
>expressing the transgenic receptor. Does anyone know to what percentage 
>this subpopulation can build up to?

There is a mechanism called Allelic Exclusion which generally prevents
more than one rearranged TCR alpha or beta chain from being expressed
at one time (same is true for rearranged Immunoglobulin light and heavy
chains.  During rearrangement in normal mice, expression of a
rearranged TCR beta or Ig heavy gene turns off rearrangement of
the other allele, and turns on rearrangement of the TCR alpha or
Ig light genes.  Expression of a TCR alpha or Ig light gene turns
off all further rearrangements.  

Since a TCR alpha or beta transgene is already rearranged, rearrangement
of the endogenous genes should never occur.  In practice, exclusion
is more complete for the TCR beta chain than TCR alpha, with beta
chain exclusion at 95% or better and alpha somewhat less.  In a TCR
alpah/beta double transgenic mouse, typically most to all T cells will
express the transgenic beta chain, and most will express the alpha chain
as well.  There is a measurable population of T cells that express the
Tg-beta and a different alpha, and a population that expresses the
Tg-beta, Tg-alpha, and a second endogenous alpha (dual T cell receptor
T cells).  The frequencies of these population varies with the mouse
and depends on things like which promoter and enhancer were used and
the site of transgene integration.

Tom Thatcher                          | You can give a PC to a Homo habilis,
University of Rochester Cancer Center | and he'll use it, but he'll use it
ttha at uhura.cc.rochester.edu           | to crack nuts.

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