derek.gray at surgery.oxford.ac.uk
Fri Feb 28 18:22:39 EST 1997
Ken Miyasaki wrote:
> I was just curious as to how immunologists viewed "MHC restriction."
> Does it really exist? Isn't it just a laboratory artifact (based upon
> measurement of secondary immune responses)? Doesn't the TCR see mainly
> the antigen and not the MHC (with greater than three orders of magnitude
> difference in affinity). So why was the 1996 Nobel Prize awarded to
> people who proposed this dual cognition stuff?
If you want a demonstration of how important MHC restriction is look no
further than allograft rejection. Direct recognition of graft MHC by
recipient T cells is the main pathway for the violent rejection
response, and it occurs because the recipient T cells "mistake" the
slightly different graft MHC molecules for self MHC molecules bearing a
foreign peptide. The actual peptide carried by the graft MHC molecules
is probably irrelevant, i.e. the T cell response will occur even if the
peptide carried on the graft MHC is identical to recipient peptide. Up
to 10% of T cells will respond to a fully MHC mismatched graft, and
without immunosuppression the violence of the reaction is awesome.
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