Major Histocompatibility

Complex (MHC)
There are three major histocompatibility
antigens; class I, classII, and class III
MHC antigens .These antigens are
genetically determined by a set of genes
called the major histocompatibility gene
complex , which lie on a portion of the short
arm of human chromosome 6.These genes
occupy four regions (A,B,C and D).
HLA (MHC) gene
• Regions B,C and A determine the antigenic
specificities of class I MHC surface
molecules.
• Region D determines the antigenic
specificities of class II MHC surface
molecules.
• The region between D and B codes for
certain complement components ( C2,C4,
factor B), and is not concerned with graft
rejection. It is called class III MHC.
• Class I MHC – antigens: are glycoproteins and
include HLA-A,HLA-B, and HLA-C. They are
found on all nucleated cells. Class I MHC
enables cytotoxic T cells (Tc) to recognize
foreign antigen on the surface of graft cells,
tumour cells or virus infected cells and kill these
cells. In other words Tc cells (CD8)are triggered
only when they recognize both antigen and class
I MHC molecules in close association on the
surface of cells. This is known as MHC-
restriction.
• Class II MHC-antigens: or HLA-D antigens are
glycoproteins, and include HLA-DP, HLA-DQ
and HLA-DR.
• These are found chiefly on the surface of T
lymphocytes, and antigen presenting cells
(APCs) such as monocytes, macrophages,
dendritic cells and B lymphocytes.
• Helper T cells (Th) (CD4) will recognize foreign
antigen on the surface of APC only if they are
associated with class II MHC molecules (MHC
restriction).
HLA (MHC)
 Class - I MHC Class - II MHC
1-They include classical 1-They include classical
HLA- A ,B , C HLA- DP ,DQ , DR
• non classical non classical
HLA- G , E HLA- DM, DO
2- Found on all nucleated cells 2-Found on certain cells
e.g. T- cells,and APCs.

3-Presents the Ag to Tc 3-Presents the Ag to Th

4-Determined by serologic tests 4-Determined by cellular tests

e.g. Microcytotoxicity tests e.g. Mixed lymphocyte reaction
• Both classes could be typed by:
ELISA, Flow cytometry or molecular
techniques such as PCR.
 Importance of MHC
1.Organ transplantation and graft rejection.
2.MHC restriction:
a) Tc cells recognize the Ag in association
with MHC I.
b) Th cells recognize the Ag in association
with MHC II.
3.Disease association: It is found that the
presence of certain HLA antigens is often
associated with a particular disease;
- HLA- B27 with ankylosing spondylitis.
- B8 with myasthenia gravis.
-DR2 with multiple sclerosis.
-DR4 with rheumatoid arthritis
4.Paternity testing and forensic
investigations
( An individual inherits one maternal and
one paternal chromosome 6).