1. MAJOR
HISTOCOMPATIBILITY
COMPLEX
PRESENTED BY PRANZLY

2. DEFINITION
• Major histocompatibility complex (MHC) is the cluster of gene
arranged within a long continuous stretch of DNA on chromosome
number 6 in Human which encodes MHC molecules.
• MHC molecule is a cell surface glycoprotein receptor present in APCs
and acts as antigen presenting structure
• The main function of MHC molecules is to bind to peptide
antigens and display them on the cell surface for recognition by
appropriate T-cells.
• In Human MHC is known as Human Leucocyte antigen (HLA)
complex.

3. THE GENES OF MHC ARE RECOGNIZED IN THREE CLASSES,
CONSEQUENTLY THERE ARE THREE TYPES OF MHC
MOLECULES.
Types
CLASS
MHC 1
CLASS
MHC 2
CLASS
MHC 3

5. CLASS MHC 1
• Class-I MHC gene encodes
glycoprotein molecule which
expressed on the surface of all
nucleated cells and platelets.
• Association of α-chain and β2
microglobulin is required for
expression of class-I MHC molecule on
cell membrane.
MHC-I
molecule
contains
α-chain
45KDa
β2-
microglobulin
molecule
12KDa

6. α-CHAIN OF CLASS MHC 1
• The α-chain is a transmembrane glycoprotein
encoded by polymorphic gene within A, B and
C region of Human HLA complex
• The α-chain is anchored in the plasma
membrane by its hydrophobic trans-
membrane segment and hydrophilic
cytoplasmic tail.
• A transmembrane domain of about 25
hydrophobic AA followed by short stretch of
charged (hydrophilic) amino acids(AA) of
cytoplasmic tails of 30 AA.
• α1 and α2 domains interacts to form a deep
groove on the top which is a peptide binding
cleft. It can binds antigen of 8-10 AA long
α-chain is
made up
of 3
domains
α1
90 amino
acids
α2
90 amino
acids
α3
90 amino
acids

7. β2-microglobulin OF CLASS MHC 1
• β2 microglobulin is a protein encoded by a highly conserved gene
located on different chromosome
• β2 microglobulin is similar in size and organization to α3 domain.
• β2 microglobulin does not contain transmembrane region and is
non-covalently linked with α-chain.

8. peptide binding cleft
CLASS MHC 1
Membrane distal
domain
Membrane proximal
Domain
(Ig fold structure)
transmembrane region
Cytoplasmic
tail

9. MECHANISM OF CLASS MHC 1
MHC class I glycoproteins present antigens of endogenous origin to
TCRs of CD8+ T cells
Endogenous peptides derive from degradation of intracellular
proteins, including viral or tumor antigens through the
PROTEOSOME.
Degradation products translocate from the cytoplasm to the
endoplasmatic reticulum (ER) where they are loaded on MHC class
I molecules via the peptide loading complex
Cellular components involved in the presentation of endogenous
antigens, from proteasome subunits to the peptide-loading
complex, are collectively referred to as antigen-processing
machinery (APM).
CD8+ T lymphocytes express CD8 receptors, the TCR fits the epitope within
the MHC class I molecule, thus CD8+ T lymphocytes triggers the cell to
undergo programmed cell death by APOPTOSIS.

10. FUNCTION OF CLASS MHC 1
1. ANTIGEN PROCESSING AND PRESENTATION
• bind endogenous peptide antigens and present to CD8+ T cells.
• CD8 T cells are specific for MHC-I antigen
2. TRANSPLANT REJECTION
During transplant of an organ or stem cells, MHC molecules
themselves act as antigens and can provoke immune response in the
recipient causing transplant rejection.

11. CLASS MHC 2
• Class-II MHC is the glycoprotein
molecule expressed primarily on
antigen presenting cells such as
macrophages, dendritic cells and B-
cells.
• Structure of class MHC 2 resemble class
MHC 1 the only difference is that
peptide binding cleft is formed by both
α-chain and β-chain.
MHC-II molecules
contains two different
polypeptide chains which
are associated by non-
covalent interactions.
α-chain
33 KDa
β-chain
28KDa

12. α-CHAIN OF CLASS MHC 2
• α-chain of MHC-II is a membrane bound glycoprotein that contains
external domains, a transmembrane segment and a cytoplasmic tail.
• α-chain are made up of two domains (α1 and α2)
• The peptide biding cleft is a open ended groove formed between α-
chain and β-chain at proximal end.
• The cleft can bind antigenic peptide of 13-18 amino acids long

13. β-CHAIN OF CLASS MHC 1
• β-chain of MHC-II is a membrane bound glycoprotein that contains
external domains
• β-chain are made up of two domains (β1 and β2)
• β-gene of some MHC class 2 can get tandemly duplicated instead of
one gene per homologues chromosome a cell can have more genes.
• Because of this one cell can simultaneously express more than two
allelic products because of this one cell can express as many as 20
MHC molecules.

14. peptide binding cleft
CLASS MHC 2
Membrane distal
domain
Membrane proximal
Domain
(Ig fold structure)
transmembrane region
Cytoplasmic
tail

15. MECHANISM OF CLASS MHC 2
They present exogenous antigen to CD4+ T cell.
Phagocytes such as (macrophage, dendritic cell) take up entities by
phagocytosis into phagosome which fuse with lysosome to form
endosome.
Class MHC 2 synthesise by endoplasmic reticulum is transported to
endosome compartment via Golgi apparatus.(α-chain and β-chain are
complexed with a polypeptide chain called invariant chain-which
prevent them to bind to endogenous peptide )
Due to acidic nature of endosome the INVARIANT CHAIN is removed
where it binds to exogenous peptide and then it is transferred to
membrane surface.
Where T helper cell with the help of CD4+ recognise it and elicit a
immune response

16. FUNCTION OF CLASS MHC 2
• MHC-II is to bind peptide antigen and present to CD4+ T
(HELPER)cells.
• MHC-II are found on surface of Antigen presenting cells (APCs).
• CD4+ T-cells are specific for MHC-II.
• Activates B cells for antibody production
• Plays a significant role in graft versus host response and in mixed
lymphocyte reaction (MLR)