Major Histocompatibility Complex
(MHC)
Prof Michelle Gordon
email: tarinm@[Link]
Major Histocompatibility Complex (MHC)
• Overview
• MHC Class I
• MHC Class II
• Summary
What is major histocompatibility
complex (MHC)?
• Histocompatibility refers to the quality of being tissue (histo)
compatible.
• Used in transplantation to describe the ability of a donor’s tissue or
organ to be accepted by a recipient.
• Are a group of genes that code for proteins found on the surfaces of all
nucleated cells.
• They present peptides made inside the cell to the immune system
(leukocytes).
• Helps the immune system recognize “self” from foreign substances.
• In humans the complex is called the human leukocyte antigen (HLA)
system. (HLA A, B and C)
MHC (cont)
• MHC Class I molecules span the membrane of almost every cell in an
organism.
– Intracellular pathogens (virus/cancer) recognized by the CD8 glycoprotein (Cytotoxic T-
cells).
• MHC Class II molecules are restricted to cells of the immune system eg,
macrophages and lymphocytes.
– Extracellular pathogens (bacteria/parasites) recognized by the CD4 glycoprotein (T-
helper cells).
• In humans these molecules are encoded by several genes all clustered in
the same region on chromosome 6. Each gene has an unusually large
number of alleles (alternate forms of a gene that produce alternate forms
of the protein).
• Therefore it is rare for two individuals to have the same set of MHC molecules
• MHC class III molecules are other proteins such as complement proteins,
cytokines (chemical messengers), and enzymes.
MHC class I
[Link]
[Link]
Function:
• Used by the leukocytes to distinguish healthy cells from
infected cells.
[Link]
Structure:
• 4 polypeptide units: α1, α2 α3 (connects to cell) and ᵝ1.
MHC CLASS I
MOLECULE
SHORT PIECE
FROM A PROTEIN
GROOVE FROM INSIDE
THE CELL
ALL NUCLEATED CELLS IN THE BODY
MHC class I (cont)
Mechanism:
• The healthy cell binds normal protein peptides (that are created
inside the cell) onto the cleft.
• Moves the peptide to the surface of the cell.
• Leukocytes recognise the “self antigen” as a normal cell.
SAMPLES OF ALL
THE PROTEINS IN
THE CELL ARE
DIGESTED INTO
SMALL FRAGMENTS
EACH FRAGMENT IS THEN
LOADED INTO THE GROOVE
OF AN MHC Class I MOLECULE
AND DISPLAYED ON THE
Figure curtesy of W .Daniels
OUTSIDE OF THE CELL
MHC class I (cont)
• In the case of an infection (eg virus):
• The infected cell also contains viral components (produced by
the virus and broken down by the host proteases).
• These bind to the cleft in the MHCI molecule and “presented”
on the surface of the cell.
• The CD8 +ve T cells recognize the foreign antigen and binds to
it, initiating an immune response
CYTOTOXIC (CD8)
T-LYMPHOCYTE
SOMATIC CELL
CD8
PRE-PERFORIN
TCR SOMATIC CELL
PEPTIDES IN THE GROOVES OF MHC I which contains
MOLECULES ARE CHECKED a foreign protein PERFORIN CANALS Figure curtesy of
(e.g. VIRUS) KILL THE SOMATIC CELL W .Daniels
MHC class II
[Link]
• Function:
MACROPHAGES IN TISSUE
• Used by the immune system to MONOCYTES IN BLOOD
communicate between different types of
leukocytes. LANGERHANS CELLS IN SKIN
• Structure: DENDRITIC CELLS IN LYMPH
• 4 polypeptide subunits: α1, α2, ᵝ1 and ᵝ2. NODES
B-LYMPHOCYTES
[Link]
MHC class II (cont)
Mechanism:
• When an immune cell, eg macrophage, engulfs a foreign
particle, eg bacterial cell, it forms a phagosome.
• Lysosomes within the phagosome break down the bacterium.
• Parts of the bacterium (antigen) bind to the MHCII molecule
and are “presented” on the cell surface. PHAGOCYTOSED PARTICLE
IS DIGESTED IN LYSOSOME
MACROPHAGE
DIGESTION PRODUCTS
PHAGOCYTOSES ARE DISPLAYED
DEBRIS IN TISSUES ("PRESENTED") ON
INCLUDING BACTERIA MHC II MOLECULES
MHC class II (cont)
• The macrophage releases Interleukin 1 T-HELPER (CD4)
LYMPHOCYTE
(IL1). APC
• IL1 calls upon the CD4 +ve T-helper CD4
cells.
• The T-cell receptor recognizes the TCR
antigen bound to the MHCII molecule and
releases IL2
• IL2 stimulates the B and T lymphocytes IF THE PEPTIDE FRAGMENT
IS FOREIGN, THEN THE
to differentiate. T CELL SECRETES:
H
• B-cells form memory and plasma cells
OR INTERFERON INTERLEUKINS
• T-cells form memory and cytotoxic T-cells & TNF 4-13
(CD8+ cells
MACROPHAGES B-LYMPHOCYTES
& CYTOTOXIC
T-LYMPHOCYTES
.
IgG, IgE etc
Summary
• MHC class I molecules span the membrane of almost every cell in an
organism.
– distinguish healthy cells from infected cells.
– Presents endogenous antigens (from inside the cell)
– 4 polypeptide units: α1, α2 α3 (connects to cell) and ᵝ1
– peptides in the grooves of MHC I molecules are checked by CD8 +ve
cytotoxic T-cells
• MHC class II molecules are restricted to cells of the immune system eg,
macrophages and lymphocytes.
– used by the immune system to communicate between different types
of leukocytes.
– Presents exogenous antigens (originated outside the cell)
– 4 polypeptide subunits: α1, α2, ᵝ1 and ᵝ2
– peptides in the grooves of MHC II molecules are checked by
CD4 positive helper T-cells
Thank You!
