Lecture 8 MHC

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
Introduction: The major histocompatibility system is a collection of molecules

(mostly proteins and glycoproteins) resident in the cytoplasm of the cell. The
complex functions mainly in the expression of antigens that are processed within a
cell for their onward presentation to appropriate T-cells to elicit immune response.
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.
Subclasses of the HLA 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).
It consists of two non-covalently linked polymorphic poplypeptide chain (α1-3),

with a molecular weight of 43,000 and another chain consisting of a non-
polymorphic polypeptide chain with molecular weight of 12,000 (β 2
microglobulin). It has a C-terminal linking its α chain that attaches it to the cell
membrane and an extracellular part comprising of three domains (α 1-3). The β2
component has semblance to immunoglobulin and is thought to be responsible
for the conveyance of newly synthesized proteins from the cytoplasm
(endoplasmic reticulum) to the cell surface. The peptides binding to it are also
thought to be uniform in their size and have between 8-10 amino acids.
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.
Features of the complex
1. Most polymorphic genetic system known to human understanding.

2. Comprises of between 24-50 alleles.
3. All the domains of the two classes are polymorphic at their N-terminal.
Functions of the system
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;
1. Determination of HLA compatibility before tissue/organ transplantation.

2. Paternity testing. This is a medico-legal situation in which the paternity of a
child is in dispute and requires medical confirmation. Simple red cell typing
is first done, but if this fails to ascertain the supposed father, HLA typing is
employed.
3. Anthropologic studies. This is employed in the distinction of a particular
population from another. It works on the principle that people from a
particular population share similar haplotypes of HLA.
4. HLA- disease establishment. The occurrence of certain disease kinds (and
susceptibility to some infections) has been associated with HLA alleles.
Some of the disease conditions implicated include; rheumatoid arthritis,
ankylosing spondylitis, Sjorgren’s disease, Hodgkin’s disease, acute
lymphocytic leukemia, idiopathic haemachromatosis, insulin dependent
diabetes mellitus, Coeliac disease, multiple sclerosis, Chron’s disease and
autoimmune hepatitis.
Figure 1. Diagrammatic presentation of MHC- classes I and II.

Lecture 8 MHC

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MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

Introduction: The major histocompatibility system is a collection of molecules

Subclasses of the HLA system

It consists of two non-covalently linked polymorphic poplypeptide chain (α1-3),

Features of the complex

1. Most polymorphic genetic system known to human understanding.

Functions of the system

1. Determination of HLA compatibility before tissue/organ transplantation.

Figure 1. Diagrammatic presentation of MHC- classes I and II.

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