An antigen-presenting cell or accessory cell is a cell that displays foreign antigens complexed
with major histocompatibility complexes on their surfaces; this process is known as antigen
presentation.
T-cells may recognize these complexes using their T-cell receptors.
These cells process antigens and present them to T-cells.
Types APCs fall into two categories: professional
or non-professional.
T cells cannot recognize, and therefore cannot respond to, 'free' antigen.
T cells can only 'see' an antigen that has been processed and presented by cells via
carrier molecules like MHC and CD1 molecules.
Most cells in the body can present antigen to CD8+ T cells via MHC class I molecules
and, thus, act as "APCs"; however, the term is often limited to specialized cells that
can prime T cells.
These cells, in general, express MHC class II as well as MHC class I molecules, and can
stimulate CD4+ T cells as well as CD8+ T cells, respectively.
To help distinguish between the two types of APCs, those that express MHC class II molecules
are often called professional antigen-presenting cells.
Professional APCs Professional APCs are very efficient at internalizing
antigen, either by phagocytosis or by receptor-mediated endocytosis, and then displaying a fragment
of the antigen, bound to a class II MHC molecule, on their membrane.
The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the
membrane of the antigen-presenting cell.
An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading
to activation of the T cell.
The expression of co-stimulatory molecules is a defining feature of professional APCs.
There are three main types of professional antigen-presenting cells:
Dendritic cells, which have the broadest range of antigen presentation, and are probably
the most important APC.
Activated DCs are especially potent TH cell activators because, as part of their composition,
they express co-stimulatory molecules such as B7.
This B7 co-stimulator of mature interdigitating dendritic cell interacts with surface CD28
of naïve T-cell.
Macrophages, which are also CD4+ cells and are therefore susceptible to infection by
HIV as well, since HIV invades immune cells through CD4+ receptor interactions.
Certain B-cells, which express and secrete a specific antibody, can internalize the antigen,
which bind to its BCR and present it incorporated to MHC II molecule, but are inefficient APC
for most other antigens.
Certain activated epithelial cells Non-professional
A non-professional APC does not constitutively express the Major Histocompatibility Complex
class II proteins required for interaction with naive T cells; these are expressed only
upon stimulation of the non-professional APC by certain cytokines such as IFN-γ.
Non-professional APCs include: Fibroblasts
Thymic epithelial cells Thyroid epithelial cells
Glial cells Pancreatic beta cells
Vascular endothelial cells Interaction with T cells
After APCs have phagocytosed pathogens, they usually migrate to the vast networks of lymph
vessels and are carried via lymph flow to the draining lymph nodes.
The lymph nodes become a collection point to which APCs such as dendritic cells can
interact with T cells.
They do this by chemotaxis, which involves interacting with chemokines that are expressed
on the surface of cells or have been released as chemical messengers to draw the APCs to
the lymph nodes.
During the migration, DCs undergo a process of maturation; in essence, they lose most
of their ability to further engulf pathogens, and they develop an increased ability to communicate
with T cells.
Enzymes within the cell digest the swallowed pathogen into smaller pieces containing epitopes,
which are then presented to T cells using MHC.
Recent research indicates that only certain epitopes of a pathogen are presented because
they are immunodominant, it seems as a function of their binding affinity to the MHC.
The stronger binding affinity allows the complex to remain kinetically stable long enough to
be recognized by T cells.
External links Antigen: protease degradation on YouTube - PMAP
The Proteolysis Map-animation Antigen-Presenting Cells at the US National
Library of Medicine Medical Subject Headings References
Kindt, TJ & Goldsby, RA, 2007, Kuby immunology, 6th ed, W.H. Freeman, New York, N.Y.