Why will MHC indicate graft as foreign?

Ian A. York iayork at panix.com
Fri Apr 18 08:10:40 EST 2003

In article <19cb9da0.0304180452.4e26bc8 at posting.google.com>,
Mikael Hanell <mikaelhanell at hotmail.com> wrote:
>The MHC has little to do to the fact that a graft is considerd forign.

Not entirely true.  That's true only if the MHC is matched, in which case 
the graft is still treated as foreign but much less agressively (because 
of minor histocompatibility antigens, which in general are "what's made in 
the cells", i.e. peptide epitopes presented on MHC.  That's the situation 
you describe in the rest of your post, and clinically it's probably the 
most common situation, because people are MHC catched before most 

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 York   (iayork at panix.com)  <http://www.panix.com/~iayork/>
    "-but as he was a York, I am rather inclined to suppose him a
     very respectable Man." -Jane Austen, The History of England

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