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Hello.
This is Jim Kaufman
from the University of Edinburgh
and the University of Cambridge,
with the first of two talks
on the MHC and MHC molecules.
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We're going to cover a variety
of topics in these two talks.
But we're going to begin
this first talk with
the definition and the central
role of MHC molecules.
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First, what is the MHC?
It stands for the major
histocompatibility complex.
It was discovered
first in mice as
a histocompatibility
two, or H-2, locus
and then in humans as HLA,
or Human Leukocyte Antigen.
These two genetic loci
were the loci that were
most responsible for
rapid graft rejection.
That's reflected in the name.
It's the major complex or region
that's responsible for the
compatibility of tissues,
which is what 'histo' means.
We now know that both of these
regions are really large
and they determine the
"transplantation antigens"
for which there are thousands
of genetic variants,
which geneticists
call "alleles".
These are the molecules
or genes that are matched
by "tissue typing"
for transplants
in order to avoid rejection
by the immune system.
H-2 and HLA are the best
characterized mammalian MHCs,
due to their importance
in biomedicine.
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It was a big puzzle
for many years
as to why this complicated
system evolved.
It has many thousands
of MHC alleles
and involves robust
immune responses
and it seemed ridiculous
that it existed
just to frustrate
transplant surgeons.
Now we know that MHC
molecules are used by
the immune system to detect
infections inside cells,
cancers and threats
outside of cells.
The high polymorphism,
that is the large
number of alleles,
is (mostly) driven by a molecular
arms race with pathogens.