|Major Histocompatibility Complex|
The Major Histocompatibility
Complex (MHC) is a group of genes that, in humans, code for a complex of
cell surface proteins called the Human
Leukocyte Antigen (HLA). The word "Histocompatibility" comes from "histo"
meaning tissue and "compatible". Any two people with the same MHC have compatible
body tissue which means that skin and organs from one will be compatible for transplant
into the other. Our immune systems will reject tissue from people with
different MHCs. Most cells in the body express MHC proteins.
In humans, MHC is equivalent to HLA and performs two essential immune
I want to concentrate on the Major Histocompatibility Complex in a little
detail because it is implicated in multiple sclerosis
in two important and closely linked ways:
Antigen Presentation which involves presenting broken down protein segments
(antigens) to certain immune system cells (T
Cells) which determine whether they belong to self or non-self tissue.
Releasing some of the messenger molecules that mediate the inflammatory
response (cytokines) and other proteins
that contribute to that response (complement).
There are three classes of MHC:
MS is believed to be an autoimmune disease
in which the immune system attacks the body's own tissue and MHC provides
the mechanism whereby the immune system determines what is the body's own
The genes most consistently associated with multiple sclerosis are found
in regions of the MHC.
Here is a simplified diagram of the human MHC genes located in a single
stretch on the short arm of chromosome 6:
MHC class I
These proteins are expressed on almost all cells in the body. In fact,
each cell will express around 100,000 MHC class I molecules. Protein fragments
(antigens) are transported from inside the cell where they are held like
a sausage in a hot dog. The MHC class I binds to a type of immune system
cell called a killer (cytotoxic) T cell
and "presents" the captured antigen to it. If the killer T Cell's receptor
matches the captured antigen, it will mount an attack on the presenting
cell, destroy it with toxic enzymes (lysis) and
tell it to kill itself (apoptosis). In this
way, killer T cells keep virus-infected or malignant cells in check.
MHC class II:
These proteins are expressed on cells of the immune system called antigen
presenting cells (APC). Examples of APCs include Dendritic
Cells, Macrophages, B
Cells, Neutrophils and Mast
Cells. Part of the function of these cells to engulf dead cells and
other material and break it down into antigens. These antigens are then
presented to helper T cells via MHC class
II in much the same way that antigens are presented to killer T cells via
MHC class I as described above.
When the Helper T cell's receptor matches the antigen, it becomes
activated and initiates the body's immune response which includes initiating
antibody production, activating killer T
cells and releasing messenger molecules, called chemokines,
which summon a variety of other immune system cells (leukocytes)
to the site of the infection.
MHC class III:
MHC class III proteins are a diverse group of molecules that perform
a variety of functions in the body. They include complement
proteins which are involved in the antibody response, the inflammatory
cytokines, tumour necrosis factor-a
and -b (TNF-a
and -b) and two
heat shock proteins which help cells deal with heat, stress and viral
C2, Hsp70, BF
Major Histocompatibility Complex links:
of the HLA region
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