MHC Molecules
MHC
molecules perform critical roles in the immune system, organising our bodies'
defence against pathogens and regulating immunological responses. These
molecules, which are classified as MHC class I and MHC class II, deliver
pathogen-derived peptides to immune cells, allowing them to identify and
eliminate intruders. The extraordinary variety of the MHC, which is shaped by
genetic variation, plays an important function in immune surveillance and
determines disease susceptibility. Furthermore, matching MHC profiles is
critical in transplantation to prevent organ rejection.
Types of MHC molecules and their
function
Major
Histocompatibility Complex (MHC) molecules, also known in humans as Human
Leukocyte Antigen (HLA) molecules, are essential components of the immune
system. They are divided into two basic classes, MHC class I and MHC class II,
with diverse activities in immunological surveillance, pathogen defence, and
autoimmune processes. We shall look at the types and functions of MHC
molecules in this detail.
I) Molecules of MHC Class I
Almost
all nucleated cells in the body have MHC class I molecules on their surface.
They are essential in immune defence because they deliver peptides produced
from intracellular pathogens, notably viruses, to cytotoxic T cells (CD8+ T
cells). The following are the essential components of MHC class I molecules:
a) Heavy Chain:
HLA-A, HLA-B, or HLA-C genes in humans encode the MHC class I heavy chain. It
is the main structure in charge of peptide binding and presentation.
b) Beta-2 Microglobulin:
This smaller protein, which is not covalently linked to the heavy chain,
stabilises the MHC class I molecule and is required for it to function
properly.
MHC
class I molecules' principal purpose is to display endogenously synthesised
antigens, which can include viral or intracellular pathogen-derived peptides,
as well as abnormal or mutant host proteins. Several important processes are
involved in the process of antigen presentation by MHC class I molecules:
1) Antigen Processing:
The proteasome, a cellular component responsible for protein degradation,
breaks down intracellular pathogens into minute peptide pieces. These peptides
are then delivered into the endoplasmic reticulum.
2) Peptide Binding:
Peptides with the right properties are chosen inside the endoplasmic reticulum
and bind to the MHC class I heavy chain in a peptide-binding groove. Only
peptides that fit snugly into this groove are shown.
3) Surface Expression:
The MHC class I molecule, now carrying its peptide payload, is transported to
the cell's surface and displayed for cytotoxic T cell monitoring.
4) T Cell Recognition:
When a cytotoxic T cell comes into contact with a cell that has MHC class I
molecules with foreign or aberrant peptides, it recognises the complex,
indicating that the presenting cell is contaminated or compromised. This
triggers an immunological response, which results in the removal of the
diseased or defective cell.
II) Molecules of MHC Class II
In
contrast to MHC class I, MHC class II molecules are typically located on the
surface of antigen-presenting cells (APCs). Dendritic cells, macrophages, and B
cells are all members of this class. MHC class II molecules specialise in
delivering extracellular pathogen-derived peptides to helper T cells (CD4+ T
cells), which are essential for coordinating immunological responses. The
following are the essential components of MHC class II molecules:
MHC
class II molecules are made up of two different chains, the alpha & beta chains, which are
encoded by the HLA-D genes in humans. These chains are joined together to form
a peptide-binding groove.
MHC
class II molecules are essential for the start of immune responses against
external pathogens including bacteria and fungus. The process of antigen
presentation by MHC class II molecules involves the following steps:
1) Antigen Uptake: Extracellular
pathogens are engulfed by antigen-presenting cells via mechanisms such as
phagocytosis or endocytosis. The pathogen is subsequently broken down into
smaller peptides within endosomes, which are specialised compartments.
2) Peptide Loading:
Pathogen-derived peptides are loaded onto MHC class II molecules, which are
also present in these compartments, in endosomes.
3) Surface Expression:
The MHC-peptide complex is transported to the cell surface and presented to
CD4+ T lymphocytes.
4) T Cell Activation:
A helper T cell recognises an APC expressing MHC class II molecules containing
pathogen-derived peptides. This contact activates the helper T cell, which can
subsequently direct an immune response against the invading pathogen. This
involves activating B cells to make antibodies, as well as recruiting and
activating cytotoxic T cells.
III) Class III MHC
MHC
class III, unlike MHC classes I and II, does not directly engage in antigen
presentation. Instead, it is made up of a collection of genes that are engaged
in numerous immunological processes. These genes encode proteins that aid in
the immune response, such as complement components and cytokines.
MHC
class III genes are not involved in antigen presentation to T cells, although
they do play key roles in inflammation and immunity.
