Lecture 8 MHC
Lecture 8 MHC
History: In the course of human development, it got to a point that it was observed
that there was rejection of tissue grafts exchanged between individuals of a
particular species. However what causes this rejection was unknown. With time,
scientists were able to unravel this component responsible for rejection of grafts as
the MHC. In humans, this complex is referred to as the Human Leucocyte Antigen
(HLA). This stemmed from the fact that about 6 decades ago, scientists observed
that either previously transfused or pregnant women developed antibodies that tend
to combat leucocytes in their serum. The HLA plays a major role in determining
whether a transplant is successful or not. The HLA system is thought to reside
in the rough endoplasmic reticulum and encoded on the short arm of chromosome
6, consisting of three regions that are responsible for the 3 classes of the complex.
Composition: there are two major components of the HLA system, with an
adjoining third component (which is more important to the complement system
than in antigen presentation). The components are termed classes and are grouped
based on their structural similarity and encoding genes. Thus, we have:
1. Major components; these are HLA classes I and II. They have structural
similarities. They are cell surface glycoproteins.
a. HLA- class I; this component is associated with the presentation of
intracellular antigens such as viruses and present antigens to T cytotoxic
(CD8) cells. Almost all somatic (nucleated) cells in vertebrates are thought
to express this class.
b. HLA- class II; this second component is associated with extracellular
antigens that have been engulfed into the cell and processed. They present
such processed antigens to T helper (CD4) cells. Their secretion is unique to
professional antigen presenting cells, such as B-cells, macrophages and
dendritic cells, and other immune cells implicated in inflammation.
2. Minor component: this is the third class of the HLA component. They lack a
role in antigen presentation but have been observed to play crucial role in the
complement system.
1. Class I; it is divided into three subclasses namely, HLA- IA, HLA- IB and
HLA- IC, and are coded by separate loci on the gene, which consist of
multiple alleles (numbering up to 50).
2. Class II; subdivided into HLA- IIDP, HLA- IIDQ and HLA- IIDR.
These non-covalently bond polypeptide chains are also coded by genes of the HLA
complex. The chains are α (molecular weight of 34,000) and β (molecular weight
of 29,000). Unlike in class I where only the α chain is attached to the cell
membrane (β2 microglobulin is not attached), the α and β chains of HLA II both
have units of the C-terminal attached to the cell surface and two extracellular
domains each.
All the HLA classes have functions that are unique to the immune response they
initiate. For instance, classes I and II determines the kind of molecules to be
secreted that will elicit a specific response, while the class III genes are
intrinsically implicated in the production and action of C 3 convertase. Their broad
functions include;