22.6: Antigen Presenting Cells (APC)
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- Ying Liu
- City College of San Francisco
Learning Objectives
- Identify the cells that are antigen-presenting cells (APCs)
- Describe the process of antigen processing and presentation with MHC I and MHC II
- Explain the role of antigen-presentation in adaptive immunity
Antigen-Presenting Cells (APCs)
All nucleated cells in the body have mechanisms for processing and presenting antigens in association with MHC molecules. This signals the immune system, indicating whether the cell is normal and healthy or infected with an intracellular pathogen. However, only macrophages, dendritic cells, and B cells have the ability to present antigens specifically for the purpose of activating T cells; for this reason, these types of cells are sometimes referred to as antigen-presenting cells (APCs) .
While all APCs play a similar role in adaptive immunity, there are some important differences to consider. Macrophages and dendritic cells are phagocytes that ingest and kill pathogens that penetrate the first-line barriers (i.e., skin and mucous membranes). B cells, on the other hand, do not function as phagocytes but play a primary role in the production and secretion of antibodies. In addition, whereas macrophages and dendritic cells recognize pathogens through nonspecific receptor interactions (e.g., PAMPs, toll-like receptors, and receptors for opsonizing complement or antibody), B cells interact with foreign pathogens or their free antigens using antigen-specific immunoglobulin as receptors (monomeric IgD and IgM). When the immunoglobulin receptors bind to an antigen, the B cell internalizes the antigen by endocytosis before processing and presentting the antigen to T cells.
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Antigen Presentation with MHC II Molecules
MHC II molecules are only found on the surface of APCs. Macrophages and dendritic cells use similar mechanisms for processing and presentation of antigens and their epitopes in association with MHC II; B cells use somewhat different mechanisms that will be described further in B Lymphocytes and Humoral Immunity . For now, we will focus on the steps of the process as they pertain to dendritic cells.
After a dendritic cell recognizes and attaches to a pathogen cell, the pathogen is internalized by phagocytosis and is initially contained within a phagosome. Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome, where degradation of the pathogen for antigen processing begins. Proteases (protein-degrading) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II (Figure \(\PageIndex{2}\)).
APCs do not present all possible epitopes to T cells; only a selection of the most antigenic or immunodominantepitopes are presented. The mechanism by which epitopes are selected for processing and presentation by an APC is complicated and not well understood; however, once the most antigenic, immunodominant epitopes have been processed, they associate within the antigen-binding cleft of MHC II molecules and are translocated to the cell surface of the dendritic cell for presentation to T cells.
Antigen Presentation with MHC I Molecules
MHC I molecules, found on all normal, healthy, nucleated cells, signal to the immune system that the cell is a normal “self” cell. In a healthy cell, proteins normally found in the cytoplasm are degraded by proteasomes (enzyme complexes responsible for degradation and processing of proteins) and processed into self-antigen epitopes; these self-antigen epitopes bind within the MHC I antigen-binding cleft and are then presented on the cell surface. Immune cells, such as NK cells, recognize these self-antigens and do not target the cell for destruction. However, if a cell becomes infected with an intracellular pathogen (e.g., a virus), protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface. This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen.
Before elimination of infected cells can begin, APCs must first activate the T cells involved in cellular immunity. If an intracellular pathogen directly infects the cytoplasm of an APC, then the processing and presentation of antigens can occur as described (in proteasomes and on the cell surface with MHC I). However, if the intracellular pathogen does not directly infect APCs, an alternative strategy called cross-presentation is utilized. In cross-presentation, antigens are brought into the APC by mechanisms normally leading to presentation with MHC II (i.e., through phagocytosis), but the antigen is presented on an MHC I molecule for CD8 T cells. The exact mechanisms by which cross-presentation occur are not yet well understood, but it appears that cross-presentation is primarily a function of dendritic cells and not macrophages or B cells.
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Key Concepts and Summary
- Antigen-presenting cells (APCs) primarily ingest pathogens by phagocytosis, destroy them in the phagolysosomes, process the protein antigens, and select the most antigenic/immunodominant epitopes with MHC II for presentation to T cells.
- Cross-presentation is a mechanism of antigen presentation and T-cell activation used by dendritic cells not directly infected by the pathogen; it involves phagocytosis of the pathogen but presentation on MHC I rather than MHC II.