I’ve already mentioned that the MHC is by far the
most diverse set of genes in the human genome.
So let’s take a few moments
to explore this diversity.
As you can see on this diagram, at the
top you can see a bar that is labeled M.
This is meant to represent the chromosome 6, which is where
the MHC in human is that you’ve inherited from your mom.
So M for maternal chromosome.
And you can see that there are the HLA Class I genes - HLA-A,
B and C, and the MHC Class II genes - HLA-DP, DQ, DR.
And these genes, as we’ve already heard vary
enormously from one individual to another.
So you might be HLA-A1 or
A2 or A3 or A4 and so forth.
And you can see that this
particular individual is HLA-A84.
So that gene will be transcribed and the HLA-A84
molecule will be put on the surface of that cell.
This individual has also inherited HLA-B8 variant;
could have had B3, B27, B64, whatever from the
mother, but in this case the mother’s gene that it’s
inherited… this individual has inherited is B8.
So it puts B8 on its surface.
And likewise, on the maternal chromosome
the variant of HLA-C is HLA-C17.
Of course there are two chromosomes, one
from the father and one from the mother.
So at the bottom we have the
paternal chromosome, from the father.
And this individual has inherited from
their father HLA-A2, HLA-B27; so they
do have B27 but it’s come from the father
rather than the mother, and HLA-C46.
So those three molecules
are put on the surface.
So for each HLA type, A or B or C, we
potentially have two different variants.
Now it may be that sometimes, an individual
is homozygous for a particular variant.
So you may have inherited both HLA-A2
from your mom and HLA-A2 from your dad.
So rather than having six different
versions, you may only have five.
Turning now to the MHC Class II
which remember is only expressed
on professional antigen presenting
cells, you can see the various
genes that have been inherited here on the maternal chromosome -
DP24, DQ91, DR4; on the paternal chromosome - DP6, DQ69 and DR4.
And these will additionally be put onto the
surface of professional antigen presenting cells.
Looking now at the centre of that diagram, you can see
some numbers that relate to the number of allelic variants.
And these are approximations based upon sequencing that’s been
carried out worldwide of the number of different possibilities.
So we’ve already mentioned
HLA-A1, A2, A3, A4 and so forth.
If you look at the right hand side
of this figure, you’ll see a number
underneath HLA-A of greater than 3000 for
the HLA α- chain, HLA Class I α-chain.
So there are a huge number of
different variants that can exist.
Now you’ll also see for the HLA β- chain
for Class I, the number is just one.
And that is because the HLA β-chain of MHC
Class I is not polymorphic, it doesn’t vary.
It’s only the α-chain that varies.
Turning now to MHC Class II and those other
numbers you can see next to α-chain and β-chain
in the middle of the diagram, you can see
that both the α-chain and the β-chain vary.
The β-chain for the DR is very variable
whereas the α-chain for the DR,
there are actually very few variants
that have been described, just seven.
But you can see that there is collectively
a huge variability in the MHC genes.