Why will MHC indicate graft as foreign?

Hobo noemail at noemail.com
Tue Jul 8 01:46:40 EST 2003

In article <b7otgg$5t9$1 at reader1.panix.com>,
 iayork at panix.com (Ian A. York) wrote:

> But in the classic form of graft rejection, the form in which MHC was
> originally defined, the MHC is mismatched and it's not because of these
> variant peptide epitopes.  What seems to happen in those cases is that a
> large subset of non-matched MHC is close enough to the recipient's MHC
> shape that it triggers T cells to recognize it, as if it was the
> recipient's own MHC with a foreign peptide.  In fact, this recognition is
> often very effective, perhaps because every single MHC complex on the
> foreign cell is interacting with a T cell receptor.  If a peptide epitope
> bound to the MHC is doing the triggering, then there are probably less
> (maybe much less) than 1% of the cell's MHC that are bound to that epitope
> and that are capable of doing the triggering.  In other words, you could
> imagine that in this situation the trigger is increased 100- or
> 10,000-fold, and the rejection is correspondingly violent.
> Ian 

I find this subject interesting and hope someone can answer my questions.

So, MHC molecules have to differ in order to differ in which protein 
strings they sample and bring to the surface. There are a very large 
number of MHCs in each person and even larger numbers of native protein 
strings they may sample. This means the total number of MHC/protein 
possibilities is extraordinarily large. How do the white blood cells 
recognize such a large number of possibilities?

I've read that cancer cells downregulate MHC expression, often to zero. 
NK cells are programmed to kill cells with zero MHC expression. I've 
read that the cancer cells avoid this by expressing MHC homologs at the 
surface, fooling the NK cells. If the immune system can be fooled so 
easily by MHC homologs, why is it so sensitive to differences in MHC 
composition between native and donated tissue?

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