Antigen-presenting cell

An antigen-presenting cell (APC) or accessory cell is a

Almost all cell types can present antigens in some way. They are found in a variety of tissue types. Dedicated antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while virus-infected cells (or cancer cells) can present antigens originating inside the cell to cytotoxic T cells. In addition to the MHC family of proteins, antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells.

Antigen-presenting cells are vital for effective adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. Antigen presentation allows for specificity of adaptive immunity and can contribute to immune responses against both intracellular and extracellular pathogens. It is also involved in defense against tumors. Some cancer therapies involve the creation of artificial APCs to prime the adaptive immune system to target malignant cells.

Types and functions

Antigen-presenting cells fall into two categories: professional and non-professional. Those that express MHC class II molecules along with co-stimulatory molecules and pattern recognition receptors are often called professional antigen-presenting cells.^[1] The non-professional APCs express MHC class I molecules.

T cells must be activated before they can divide and perform their function. This is achieved by interacting with a professional APC which presents an antigen recognized by their T cell receptor. The APC involved in activating T cells is usually a dendritic cell. T cells cannot recognize (and therefore cannot respond to) "free" or soluble antigens. They can only recognize and respond to antigen that has been processed and presented by cells via carrier molecules like MHC molecules. Helper T cells can recognize exogenous antigen presented on MHC class II; cytotoxic T cells can recognize endogenous antigen presented on MHC class I. Most cells in the body can present antigen to CD8+ cytotoxic T cells via MHC class I; however, the term "antigen-presenting cell" is often used specifically to describe professional APCs. Such cells express MHC class I and MHC class II molecules and can stimulate CD4⁺ helper T cells as well as cytotoxic T cells.^[2][3]

APCs can also present foreign and self lipids to T cells and natural killer cells by using the CD1 family of proteins, which are structurally similar to the MHC class I family.^[4]

Professional APCs

Professional APCs specialize in presenting antigens to T cells.^[5] They are very efficient at internalizing antigens, either by phagocytosis (e.g. macrophages), or by receptor-mediated endocytosis (B cells), processing the antigen into peptide fragments and then displaying those peptides (bound to a class II MHC molecule) on their membrane.^[1] 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 and MHC class II are defining features of professional APCs.^[1] All professional APCs also express MHC class I molecules as well.^[2]

The main types of professional antigen-presenting cells are dendritic cells, macrophages and B cells.^[1]

Dendritic cells (DCs)

Dendritic cells have the broadest range of antigen presentation and are necessary for activation of naive T cells.^[1] DCs present antigen to both helper and cytotoxic T cells. They can also perform cross-presentation, a process by which they present exogenous antigen on MHC class I molecules to cytotoxic T cells. Cross-presentation allows for the activation of these T cells.^[2] Dendritic cells also play a role in peripheral tolerance, which contributes to prevention of auto-immune disease.^[6]

Prior to encountering foreign antigen, dendritic cells express very low levels of MHC class II and co-stimulatory molecules on their cell surface. These immature dendritic cells are ineffective at presenting antigen to T helper cells. Once a dendritic cell's pattern-recognition receptors recognize a pathogen-associated molecular pattern, antigen is phagocytosed and the dendritic cell becomes activated, upregulating the expression of MHC class II molecules. It also upregulates several co-stimulatory molecules required for T cell activation, including CD40 and B7. The latter can interact with CD28 on the surface of a CD4⁺ T cell.^[2][7][8] The dendritic cell is then a fully mature professional APC. It moves from the tissue to lymph nodes, where it encounters and activates T cells.^[1]

Macrophages

Non-professional antigen presenting cells include all nucleated cell types in the body. They use an MHC class I molecule coupled to beta-2 microglobulin to display endogenous peptides on the cell membrane. These peptides originate within the cell itself, in contrast to the exogenous antigen displayed by professional APCs using MHC class II molecules. Cytotoxic T cells are able to interact with endogenous antigen presented using an MHC class I molecule.^[2] Non-professional APCs do not typically express MHC class II molecules. However, it has been observed that antigen presentation to CD4⁺ cells via MHC class II is not restricted to the classically professional APCs. Other leukocytes, including granulocytes such as mast cells and neutrophils, can be induced to do so, as can endothelial and epithelial cells under certain circumstances. Even so, there is little evidence that these atypical APCs are able to activate naive CD4⁺ T cells.^[1]

Interaction with T cells

After dendritic cells have phagocytosed pathogens, they usually migrate to the vast network of

A dendritic cell that interacts with an already-activated helper T cell can become licensed.[13] This occurs through the interaction of co-stimulatory molecules including B7 and CD40 on the dendritic cell, with CD28 and CD40 ligand on the T cell. Only licensed dendritic cells are able to activate cytotoxic T cells. T cell licensing of dendritic cells is key for activation of cytotoxic T cells for many pathogens, although the extent to which T cell help is needed may vary.^[14]

In MHC class I and class II molecules, only certain epitopes of an internalized peptide can be presented. These epitopes are termed immunodominant.^[15]

In cancer therapy

APCs naturally have a role in fighting tumors, via stimulation of B and cytotoxic T cells to respectively produce antibodies against tumor-related antigen and kill malignant cells. Dendritic cells, presenting tumor-specific antigen to T cells, are key to this process. Cancer therapies have included treating the patient with increased numbers of dendritic cells or cancer-specific T cells. However, newer therapies have turned to genetically engineered artificial antigen-presenting cells designed to prime the immune system to attack malignant cells. Some artificial APCs are derived from human cells; others are acellular, containing MHC proteins, co-stimulatory molecules and the necessary peptides.^[16][17]

The APC activator

Further reading

• Kindt TJ, Goldsby RA (2007). Kuby immunology (6 ed.). W.H. Freeman.

External links

Wikimedia Commons has media related to Antigen-presenting cells.

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