Adaptive
Immunity And Antigen Presentation
The adaptive immune system
The adaptive immune system is more specific than the innate system, and
can amplify and increase the specificity of the immune response. The main
protagonists are antigen-presenting cells (APCs), B cells and T cells. Each of
these cell types has a different function and can be identified by the
expression of a number of specific surface molecules which have been designated
with CD (cluster of differentiation) numbers. Thus, B cells can be identified
by the expression of CD19 and CD20, and T cells by the expression of CD2 and
CD3.
The adaptive immune response has two arms, the humoral arm
(antibody-mediated) and the cellular arm (principally mediated by cytotoxic T
cells [TC], which express the molecule CD8). At the centre of both
arms are T helper cells (TH), which express CD4.
CD4 T cells can be activated only when they ‘see’ peptide antigen
displayed in the groove of a specific family of glycoproteins, the major
histocompatibility complex (MHC) class II molecules (also known as human
leucocyte antigens [HLAs]). Each CD4 T cell has a unique T cell receptor (TCR),
which allows it to recognise a specific peptide-MHC II complex, and CD4 acts as
a co-receptor to stabilise the interaction between TCR and MHC. The expression
of MHC class II molecules is limited to three main cell types, which are known
as professional APCs:
1
Dendritic cells (DCs)
2
B cells
3
Macrophages (less efficient APCs).
These APCs have the ability to internalise protein antigens present
outside of the cell. APCs have different sorts of receptors, which allow them
to internalise antigen. B cells bind antigen via their B cell receptor (BCR),
which is specific for that particular antigen. In contrast, DCs and macrophages
internalise molecules via a number of receptors that are not antigen-specific,
for example FcγRs or complement receptors. They can also internalise antigen
via endocytosis.
Once internalised, these antigens are then processed within intracellular
compartments (endosomes or lysosomes) and degraded into peptides. The endosome
fuses with an exosome containing MHC class II molecules (derived from the golgi
body of the cell). Peptides are subsequently loaded into the groove of specific
class II molecules into which they specifically fit. Peptide- loaded class II
molecules are then transported to the surface of the cell where they are
accessible to CD4 T cells.
In addition to presenting antigen to CD4 T cells, APCs also provide
co-stimulatory signals to allow full activation (see Chapter 9). This involves the interaction of pairs
of molecules, one found on the
surface of the T cell and the other on the APC.
Once a CD4 T cell is activated, it may provide help to B cells through
the production of cytokines (principally IL-4) and through contact-dependent
signals, initiating a humoral response. Thus, the interaction between a B cell
and a T cell is a two-way process of mutual help and activation. Alternatively,
CD4 T cells may provide help to CD8 T cells and macrophages via the production
of a different set of cytokines (principally interferon-γ), initiating a
cellular response.
CD8 T cells can only be activated when they ‘see’ peptide antigen
displayed in the groove of an MHC class I molecule. Each CD8 T cell has a
unique TCR, which allows it to recognise a specific peptide-MHC I complex.
Almost all cell types express MHC class I molecules. In contrast to MHC class
II molecules, the anti- gens displayed on class I molecules are not obtained
from outside the cell, but rather from the cytoplasm of the cell. Thus, in the
case of a viral infection, viral antigen samples from the cytoplasm will be
processed, loaded onto class I molecules and sent to the surface of the cell to
allow detection by CD8 T cells.
Antigen presentation in transplantation
In transplantation, direct and indirect alloantigen presentation occur.
These can be defined as follows.
1
Direct antigen presentation – donor
antigen is presented on donor MHC class I or class II molecule. Between 5 and
10% of the recipient’s T cell repertoire may recognise foreign MHC, there- fore
this form of antigen presentation is very important in initiating transplant
rejection.
2
Indirect antigen presentation – donor
antigen is presented on recipient MHC class II molecule, which has been
processed by the recipient APC in the
conventional way.
