00:01
The MHC is the major
histocompatibility complex.
00:08
It’s called that because it’s a complex
of genes, it’s not a single gene.
00:13
And it’s a complex of genes that are the major determinants
of tissue compatibility during transplantation.
00:21
That’s how it was first discovered.
00:23
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.
00:40
Well of course, MHC did not evolve to
frustrate attempts at transplantation.
00:46
It’s a consequence of the diversity of
the MHC but it’s not why we have an MHC.
00:51
We have MHC to show protein antigens
in the form of peptides to T-cells.
00:58
In each individual species, the
MHC is given a particular name.
01:02
You only need to really know
about two of them.
01:05
In the human, it’s called HLA.
01:08
And in the mouse, it’s called H-2.
01:11
It’s worth knowing that because a lot of
immunology is worked out in the mouse.
01:15
So when you’re reading textbooks and so
forth, you may often come across H-2.
01:19
It’s simply the MHC of the mouse,
just like HLA is the MHC of the human.
01:28
There are two classes of MHC -
MHC Class I and MHC Class II.
01:36
And they are very similar in structure and very
similar in what they do as we’ll learn very shortly.
01:43
There are three types of MHC Class I
in the human: HLA-A, HLA-B and HLA-C.
01:52
And for Class II we have
HLA-DP, HLA-DQ and HLA-DR.
02:00
The MHC Class I molecules are present
on all nucleated cells in the body.
02:05
That’s essentially all cells in the
body apart from red blood cells.
02:11
However, the MHC Class II is only present
on a very limited number of cell types.
02:17
Essentially professional antigen
presenting cells, which are the dendritic
cells, the macrophages and the
B-cells, and on thymic epithelium.
02:27
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.
02:50
So it’s not an alternative,
it’s an addition to the Class I.
02:54
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.
03:10
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.
03:24
Let’s explore the MHC gene locus.
03:28
We’ve already heard that there are two
classes of MHC - MHC Class I and Class II.
03:34
In the humans, these genes
are present on chromosome 6.
03:40
HLA Class I consists of HLA-A,
-B and -C as we’ve heard.
03:47
And they’re actually
arranged in this order.
03:49
You may think that there’s misordering here, looks
a bit odd doesn’t it, it’s not ABC, it’s BCA.
03:56
And that’s simply the order that these
genes are present on the chromosome.
04:01
And the Class II genes for DQ, DQ, DR.
04:07
In fact there’s another region within
the MHC that’s called MHC Class III.
04:12
These genes do not actually encode
antigen presenting molecules.
04:16
So they’re really nothing much to do with
what we’re talking about at the moment.
04:20
But actually they do encode molecules
that are part of the immune response.
04:25
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.