MHC
(Major Histocompatibility Complex)
Dr. Mahfuza Nasrin
Associate Professor
Department of Microbiology
UAMCH
Definition:
MHC
MHC ( Major Histocompatibility Complex ) is a tightly
linked cluster of genes, that encode production of major
histocompatibility antigen on the cell surface.
It play a role in intercellular recognition and discrimination
between self and non-self.
The MHC antigens are called human leucocytic antigen
(HLA) because these were initially detected on leucocytes.
These proteins are alloantigen, i.e. They differ the among
members of same species.
Location of MHC genes:
All the MHC genes are located on the short arm of
chromosome number 6 in human.
MHC is divided into 3 regions:
Each region contains some compartments known as locus.
Locus means the position where a particular gene is located on
the chromosome.
CLASS I MHC consists of-
3 loci- HLA- A
HLA- B
HLA- C
CLASS II MHC consists of-
3 loci- HLA- DR
HLA- DQ
HLA- DP
All these are present within HLA –D region of MHC complex
CLASS III MHC consists of-
C2 ,C4, TNF and lymphotoxin.
Classification of MHC and their Location
1. Class-I MHC (HLA antigen)– HLA-A, HLA-B and HLA-C
genes code for Class-I MHC .
Location-These are expressed on the surface of nearly all
nucleated cells.
2. Class-II MHC (HLA antigen)– – consist of HLA-DP, HLA- DQ
and HLA-DR.
Location-These are expressed on antigen presenting cells.
Eg- Macrophages, Dendritic cells and B cell
3. Class-III MHC- (HLA antigen)– genes
encode various secreted proteins including
C2, C4, Factor B, TNF that have immune
function.
Polymorphism of MHC molecules.
Each person has two haplotype (i.e., two sets of these
genes- one on paternal and other on the maternal
chromosome 6). Each person can have as many as 12
different HLA proteins.
These genes are very diverse (polymorphic). The MHC
molecules expressed by one individual may differ
significantly from another individual of the same species.
.
The diversity of MHC is due to presence of multiple alleles at
a given genetic locus.
There are 3900 HLA-A alleles, 4800 HLA-B alleles, 3500
HLA-c alleles and more than 4600 HLA-D alleles.
However an individual inherits only a single allele at each
locus from each parent.
MHC restriction
The ability of T cell to recognize antigen is dependent
on association of the antigen with either class I or
class II proteins.
CD8+ T cells recognised antigen in association of with
class I MHC protein.
CD4+ T cells recognised antigen in association of with
class II MHC protein.
This requirement to recognise antigen in association
with a self MHC protein is called MHC restriction.
Structure
Class-I molecule consists of-
- a heavy peptide α-chain associated with a short
polypeptide called β2 microglobulin.
- α-chain is organized into 3 globular domain which
protrude from the cell surface.
Class-II molecule is formed by-
- polypeptides α & β chains
-which are similar in size & both
are anchored in surface membrane.
Antigen presentation-
Endocytic pathway (Class II MHC pathway)
- For exogenous antigens (extracellular
microorganisms)
Cytosolic pathway (Class I MHC pathway)-
For endogenous antigens is produced within
the cell (e.g. Virus infected cell) of the host.
Difference between Class I and Class II MHC
Properties Class I Class II
Stucture one polypeptides β2 microglobulin two polypeptides
Loci HLA- A HLA- DR
HLA- B HLA - DQ
HLA- C HLA – DP
Tissue All nucleated Restricted to APC
distribution cells
Function Presents Presents
processed processed
antigenic antigenic
fragments to fragments to
CD8 T cells CD4 T cells
Function of MHC molecules:
1. Regulation of immune response:
MHC class-I molecules is presentation of peptide antigen
to cytotoxic T cells.
Class-II MHC molecules present processed antigenic peptide
to TH cells.
2. Association of HLA with disease:
Certain disease show significant association with particular
HLA antigen
3. Role in organ transplantation:
The Success of organ transplantation determined by the
compatibility of the MHC gene of the donor and recipient.
Association of HLA allele with a risk of
disease susceptibility
Disease Risk Associated HLA allele
Ankylosing spondylitis, Uveitis B27
Reiter’s syndrome
Juvenile Rheumatoid arthritis DR4
IDDM DR3,DR4
SLE DR2,DQ
Myasthenia gravis DR5
HLA Typing:
Identification of HLA antigens is known as
tissue typing.
Methods for tissue typing are:
1. Serologic method,
2. Cellular method
3. DNA analysis by PCR.
Thank You
