Major Histocompatibility Complex

(MHC)

1
 INTRODUCTION
– Major Histocompatibility complex (MHC) is set of surface proteins
located on the cell membrane of nucleated cells.
– Cluster of genes found in all mammals encoding a group of highly
polymorphic cell membrane glycoprotein.
– Known as transplantation antigen or histocompatibility molecule.
– It plays more important work to identify the antigen between self and
non
self body( discriminating self/non-self) , intracellular recognition and
responsible for antigen presentation.
– Histo refers to tissues. Compatibility refers to living together
harmoniously.
–
Major Histocompatibility Complex

• It is a recognition molecule of antigen.

• Act as antigen presenting structures, it binds antigen fragments
and display them to various cells of the immune system, most
importantly T-cells.
• In human MHC is found on the short arm of chromosome 6 near
the centromere and referred to as HLA complex( Human
Leukocyte Antigen )

3
 Types
• There are three types of MHC protein molecules:
• Two major types:
1- Class I MHC molecules
2-Class II molecules.
• The MHC also contains a variety of genes that code for other proteins—
such as: complement proteins, cytokines, TNF, heat shock proteins and
enzymes—that are called
3- Class III MHC molecules
4
• The two types of MHC are worked in immunity. T helper (Th)

cells are recognized by MHC molecules II, and T cytotoxic

(Tc) cells are recognized by MHC I molecules.

5
 MHC Polymorphism
• MHC is the most polymorphic system in the body
• Each gene has an unusually large number of alleles (alternate
forms of a gene that produce alternate forms of the protein).
• As a result, it is very rare for two individuals to have the
same set of MHC molecules, which are collectively called a
tissue type.

6
 Inheritance

• Inherited as two sets (one from father and one from

mother)
• Haplotype refers to set from mother or father
• MHC are co-dominantly expressed (both mother and
father alleles are expressed).

7
Codominance

8
9
 MHC GENES
• Class I MHC Genes Found In Regions A, B and C In Humans.
• Class II MHC Genes Found In Regions DR, DP and DQ.
• Class I and Class II MHC Share Structural Features
• Both involved in antigen presentation.
• Class III MHC genes have no structural similarity to Class I
and II

10
Structures OF MHC Classes

11
 MHC-I
• Found in every nucleated cell .They are not found in Red Blood Cells.
• Consist of 3 a chains and a variable b2 microglobulin (encoded by
gene in chromosome 15).
• They have extracellular portion which form a cleft between a1- a2
which can bind peptides of 8 -10 amino acids.
• The a3 segment of the MHC I serves as a binding site for CD8.

12
13
 MHC-II
• Class II are composed of 2 non-covalent associated peptides, a chain and b
chain.
• The peptide binding cleft can accommodate peptides up to 30 amino acids
in length.
• The b2 is the binding site for the CD4(Helper) T-cells
• Involved in Ag presentation to T helper cells.
• Restricted to certain cells( the macrophages, dendritic cells and B
lymphocytes).
• Some other cells can express it when it is stimulated by INF gamma at site
of inflammation eg: T lymph, thyroid epith, pancreatic cells, renal tubules,
etc.. 14
15
 The Role Of MHC
• Immune recognition by:
1- Binding of antigen peptides (or in some cases non peptidic molecules)
2- Interaction with T cells, usually via the T-cell receptor (TCR).

16
Antigen Presentation

Antigen presentation to
T-cell
.

17
18
19
MHC I VERSUS MHC II

• The MHC-I and MHC-II molecules show preferential

restriction to T cells of the CD8- or CD4-bearing
subsets.
• This is related to the observation that CD8 binds to
MHC-I molecules, while CD4 interacts with MHC-II.

20
Transplant Rejection

• The rapid and very potent cell-mediated immune response to the

transplanted tissue results from a large number of T cells that are
specifically reactive to non-self.

21
HLA Antigens and Diseases

• There are several association between HLA antigen and disease

state the most impressive is in Ankylosing spondiolytis which
express HLA-B27
• Most autoimmune diseases are associated with particular HLA
profile eg: HLA-B8, DR2, DR3 or DR4.

22
Detection OF HLA System:

• By HLA typing:
1- Serological typing.
2- Molecular( DNA) typing: The most frequently used
methods in the HLA typing

23
24