Chapter 9 -The MHC in the Immune Response

Figure 9.1 describes the nature of the MHC proteins (MHC antigens):

The human MHC is called HLA Ð which stands for Human Leukocyte Antigen.  We often refer to them as HLA antigens.  (In the mouse they are called H-2 antigens.)

For the moment, letÕs only look at the human, shown in the top half of this figure.

As we have discussed, there are two types of MHC antigens:

Class I MHC antigens

Class II MHC antigens

Both are shown in this picture:  Note that both the genes and the proteins are shown in this figure.

There are three class II MHC proteins in humans:

HLA-DP

HLA-DQ

HLA-DR

Each of these proteins is made up of two chains - an a-chain and a b-chain.  (Each chain needs one gene.)

Another view of the MHC Class II protein structure is shown in figure 9.4

Class II MHC are only found on "professional antigen-presenting cells"

There are three human class I MHC proteins:

HLA-A

HLA-B

HLA-C

Each of these proteins is made up of two chains - an a-chain and a small polypeptide called b2 microglobulin.  (Note that the b2 microglobulin gene is not found in the MHC gene complex).

Another view of the MHC class I protein is shown in figure 9.3

Class I MHC molecules are found on all nucleated cells of the body.  Thus, all nucleated cells can present antigen to CD8(+) T-cells.

MHC proteins are essential to antigen processing and antigen presentation.

Class II proteins present pieces of exogenous antigens.  These are antigens that are ingested (or phagocytosed) by "professional" antigen presenting cells (APC's).  Processed antigen fragments are then presented to CD4(+) T-cells. 

This is diagramed in figure 9.5:

Class I proteins present pieces of endogenous antigens.  These are antigens that are made by the cell itself - antigens that come from within the antigen presenting cell.  These are usually thought of as cells that are infected with virus or some other intracellular parasite.  Such processed antigen fragments are then presented to CD8(+) T-cells.

This is diagramed in figure 9.7:

There are many alleles for each of the 6 human MHC proteins.  Since we are diploid, we have two genes for each protein.  Thus, most of us have a unique group of HLA proteins.  This is vitally important to consider when tissue transplantation is planned.

Some proteins made by bacteria and viruses have the ability to bind to MHC proteins without being processed and then activate extraordinarily large numbers of T-cells Ð up to 10% of all the T-cells in the body!  Such superantigens are capable of triggering life-threatening toxic reactions as a consequence of this abnormal T-cell activation.

Certain HLA proteins are associated with either susceptibility or resistance to specific infectious diseases. 

Certain HLA proteins are associated with autoimmune diseases.  This is indicated in Table 12.1 on page 172.