thumb|350px|right|Antigen presentation stimulates immature T cells to become either mature "cytotoxic" CD8+ cells or mature "helper" [[CD4+ cells.]]

An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells.

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.

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.

Professional APCs

Professional APCs describe those APCs which are capable of delivering all 3 signals needed to activate a naive T cell (signal 1- the antigen itself, the peptide-MHC complex; signal 2 - costimulatory ligand; signal 3- cytokines to guide polarization of the T cell). Canonically, the 3 pAPC types are dendritic cells, macrophages, and B cells. 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. All professional APCs also express MHC class I molecules as well.

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<sup>+</sup> T cell. 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. After this activation, macrophages are able to express MHC class II and co-stimulatory molecules, including the B7 complex and can present phagocytosed peptide fragments to helper T cells. Deriving from monocytes, a type of white blood cell, they will circulate in the blood and enter affected sites and differentiate from monocytes to macrophages. At the affected site, the macrophage surrounds the site of infection or tissue damage with its membrane in a mechanism called phagocytosis.

B cells

B cells can internalize antigen that binds to their B cell receptor and present it to helper T cells.

B cells reside in the lymph node. Once their B cell receptor binds to an antigen, they can interact with activated helper T cells, as described above.

A dendritic cell that interacts with an already-activated helper T cell can become licensed. 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.

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

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.

The APC activator IMP321 is being tested in clinical trials to accelerate the immune reaction to eliminate metastatic breast cancer or melanoma.

References

Further reading

  • – PMAP animation