The MHC is the major
It’s called that because it’s a complex
of genes, it’s not a single gene.
And it’s a complex of genes that are the major determinants
of tissue compatibility during transplantation.
That’s how it was first discovered.
When people were exploring, doing skin grafts for example in
mice, between different strains of mice, they recognized that the
skin graft from a different strain of mouse would be rejected,
immunologically rejected due to
recognition of these MHC molecules.
Well of course, MHC did not evolve to
frustrate attempts at transplantation.
It’s a consequence of the diversity of
the MHC but it’s not why we have an MHC.
We have MHC to show protein antigens
in the form of peptides to T-cells.
In each individual species, the
MHC is given a particular name.
You only need to really know
about two of them.
In the human, it’s called HLA.
And in the mouse, it’s called H-2.
It’s worth knowing that because a lot of
immunology is worked out in the mouse.
So when you’re reading textbooks and so
forth, you may often come across H-2.
It’s simply the MHC of the mouse,
just like HLA is the MHC of the human.
There are two classes of MHC -
MHC Class I and MHC Class II.
And they are very similar in structure and very
similar in what they do as we’ll learn very shortly.
There are three types of MHC Class I
in the human: HLA-A, HLA-B and HLA-C.
And for Class II we have
HLA-DP, HLA-DQ and HLA-DR.
The MHC Class I molecules are present
on all nucleated cells in the body.
That’s essentially all cells in the
body apart from red blood cells.
However, the MHC Class II is only present
on a very limited number of cell types.
Essentially professional antigen
presenting cells, which are the dendritic
cells, the macrophages and the
B-cells, and on thymic epithelium.
And in fact, these professional antigen presenting cells are
defined as such by having MHC Class II on their surface.
Now I’ve already mentioned that Class I is
present on all nucleated cells in the body.
And of course dendritic cells, macrophages, B-cells,
thymic epithelium, they’re nucleated cells as well.
So these cells have both MHC
Class I and MHC Class II.
So it’s not an alternative,
it’s an addition to the Class I.
The function of MHC Class I is to
alert CD8+ cytotoxic T-cells to the
presence of intracellular antigens; for
example, a virus infecting a cell.
Whereas MHC Class II is specialized
to alert CD4+ helper T-cells and CD4+
regulatory T-cells to the presence of
extracellular antigens such as bacteria.
Let’s explore the MHC gene locus.
We’ve already heard that there are two
classes of MHC - MHC Class I and Class II.
In the humans, these genes
are present on chromosome 6.
HLA Class I consists of HLA-A,
-B and -C as we’ve heard.
And they’re actually
arranged in this order.
You may think that there’s misordering here, looks
a bit odd doesn’t it, it’s not ABC, it’s BCA.
And that’s simply the order that these
genes are present on the chromosome.
And the Class II genes for DQ, DQ, DR.
In fact there’s another region within
the MHC that’s called MHC Class III.
These genes do not actually encode
antigen presenting molecules.
So they’re really nothing much to do with
what we’re talking about at the moment.
But actually they do encode molecules
that are part of the immune response.
So complement component C4,
complement component Factor B that’s
part of the alternative pathway of
complement activation, complement
component C2, lymphotoxin which is a cytokine and another
cytokine, TNF-α, are all encoded
within the MHC Class III region.
But we’re going to focus our attention now on the MHC
Class I and Class II antigen presenting molecules.