Antigen-presenting cell

Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells.

See also: Antigen presentation

An antigen-presenting cell (APC) or accessory cell is a cell that displays foreign antigen complexed with MHC on its surface. T-cells may recognize this complex using their T-cell receptor (TCR).

Types

APCs fall into two categories: professional or non-professional.

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 those specialized cells that can prime T cells (i.e., activate a T cell that has not been exposed to antigen, termed a naive T cell). These cells, in general, express MHC class II as well as MHC class I molecules, and can stimulate CD4⁺ ("helper") cells as well as CD8⁺ ("cytotoxic") T cells.

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

These 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.

There are three main types of professional antigen-presenting cell:

• Dendritic cells, which have the broadest range of antigen presentation, and are probably the most important APC. Activated DCs are especially potent T_H cell activators because, as part of their composition, they express co-stimulatory molecules such as B7.
• Macrophages, which are also CD4+ and are therefore also susceptible to infection by HIV.
• B-cells, which express antibody, can very efficiently present the antigen to which their antibody is directed, but are inefficient APC for most other antigens.

Non-professional

A non-professional APC does not constitutively express the Major histocompatibility complex 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 (skin)
• Thymic epithelial cells
• Thyroid epithelial cells
• Glial cells (brain)
• Pancreatic beta cells
• Vascular endothelial cells

Interaction with T cells

After the APCs phagocytose pathogens, they usually migrate via vast networks of lymph vessels to arrive at draining lymph nodes (this network is collectively known as the Lymphatic system). 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 (eg. endothelial cells of the high endothelial venules) 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, possibly 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.

QUERY

Some books mention activated T cells as Antigen Presenting Cells. There is no theoretical proof to back this yet. T cells don't express MHC II on their surface, nor can they process exogenously-derived proteins (so far as we know!), so they most likely don't act as professional antigen presenting cells. However, like all other nucleated cells, they express MHC I, which allows them to present endogenous antigen to CD8 (Cytotoxic) T cells, which makes them non-professional antigen presenting cells. The language can be confusing, so when I teach this, I use APC to refer only to professional APC since that is the most important distinction. I leave out the phrase 'non-professional APC' altogether when discussing nucleated cells presenting endogenous antigen in MHC I.

External links

• Antigen: protease degradation - PMAP The Proteolysis Map-animation
• Antigen-Presenting+Cells at the U.S. National Library of Medicine Medical Subject Headings (MeSH)