Antigen-presenting cell


An antigen-presenting cell APC or accessory cell is a cell that displays antigen complexed with major histocompatibility complexes MHCs on their surfaces; this process is known as antigen presentation T cells may recognize these complexes using their T cell receptors TCRs These cells process antigens and present them to T-cells

Almost all cell types can serve as some form of APC They are found in a variety of tissue types Professional antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while other cell types 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

Contents

  • 1 Types and functions
    • 11 Professional
      • 111 Dendritic cells DC
      • 112 Macrophages
      • 113 B cells
    • 12 Non-professional
  • 2 Interaction with T cells
  • 3 In cancer therapy
  • 4 References
  • 5 External links

Types and functionsedit

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 cells1 The non-professional APCs express MHC class I molecules

T cells must be activated by interacting with a professional APC presenting an antigen which their T cell receptor recognizes before they can divide and perform their function 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 cells23

APCs can also present foreign and self lipids to T cells and NK cells by using the CD1 family of proteins, which are structurally similar to the MHC class I family4

Professionaledit

Professional APCs specialize in presenting antigen to T cells5 They are very efficient at internalizing antigens, either by phagocytosis macrophages and dendritic cells 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 membrane1 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 APCs1 All professional APCs also express MHC class I molecules as well2

The main types of professional antigen-presenting cells are dendritic cells, macrophages and B cells1

Dendritic cells DCedit

Dendritic cells have the broadest range of antigen presentation and are necessary for activation of naive T cells1 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 cells2 Dendritic cells also play a role in peripheral tolerance, which contributes to prevention of auto-immune disease6

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 cell278 The dendritic cell is then a fully mature professional APC It moves from the tissue to lymph nodes, where it encounters and activates T cells1

Macrophagesedit

Macrophages can be stimulated by T cell secretion of interferon gamma9 After this activation, macrophages are able to express MHC class II and co-stiumulatory molecules, including the B7 complex and can present phagocytosed peptide fragments to helper T cells78 Activation can assist pathogen-infected macrophages in clearing the infection10

B cellsedit

B cells can internalize antigen that binds to their B cell receptor and present it to helper T cells1 Unlike T cells, B cells can recognize soluble antigen for which their B cell receptor is specific They can then process the antigen and present peptides using MHC class II molecules When a T helper cell with a TCR specific for that peptide binds, the B cell marker CD40 binds to CD40L on the T cell surface When activated by a T cell, a B cell can undergo antibody isotype switching, affinity maturation, as well as formation of memory cells2

Non-professionaledit

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 molecule2 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 cells1

Interaction with T cellsedit

After dendritic cells have phagocytosed pathogens, they usually migrate to the vast network of lymph vessels and are carried by lymph flow to the draining lymph nodes Each lymph node is a collection point where APCs can interact with T cells1 During the migration, DCs undergo a process of maturation: they lose most of their ability to further engulf pathogens and they mature by changing surface expression of MHC and co-stimulatory molecules, as well as increased production of cytokines The internalized antigen is digested into smaller peptides containing epitopes, which are then presented to T cells by the MHC211

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 vary12

In MHC class I and class II molecules, only certain epitopes of an internalized peptide can be presented These epitopes are termed immunodominant13

In cancer therapyedit

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 peptides1415

Referencesedit

  1. ^ a b c d e f g h i Kambayashi, Taku; Laufer, Terri M "Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell" Nature Reviews Immunology 14 11: 719–730 doi:101038/nri3754 
  2. ^ a b c d e f g den Haan, Joke MM; Arens, Ramon; Zelm, Menno C van "The activation of the adaptive immune system: Cross-talk between antigen-presenting cells, T cells and B cells" Immunology Letters 162 2: 103–112 doi:101016/jimlet201410011 
  3. ^ Hivroz, Claire; Chemin, Karine; Tourret, Marie; Bohineust, Armelle "Crosstalk between T Lymphocytes and Dendritic Cells" Critical Reviews™ in Immunology 32 2: 139–155 doi:101615/critrevimmunolv32i230 
  4. ^ Barral, Duarte C; Brenner, Michael B "CD1 antigen presentation: how it works" Nature Reviews Immunology 7 12: 929–941 doi:101038/nri2191 
  5. ^ Mann, Elizabeth R "Intestinal antigen-presenting cells in mucosal immune homeostasis: Crosstalk between dendritic cells, macrophages and B-cells" World Journal of Gastroenterology 20 29: 9653 PMC 4123356  PMID 25110405 doi:103748/wjgv20i299653 
  6. ^ Mbongue, Jacques; Nicholas, Dequina; Firek, Anthony; Langridge, William 2014-04-30 "The Role of Dendritic Cells in Tissue-Specific Autoimmunity" Journal of Immunology Research 2014: 1–17 PMC 4022068  PMID 24877157 doi:101155/2014/857143 
  7. ^ a b Mittal, Sharad K; Roche, Paul A "Suppression of antigen presentation by IL-10" Current Opinion in Immunology 34: 22–27 PMC 4444374  PMID 25597442 doi:101016/jcoi201412009 
  8. ^ a b Brzostek, Joanna; Gascoigne, Nicholas R J; Rybakin, Vasily 2016-01-01 "Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition" T Cell Biology 7: 24 PMC 4740375  PMID 26870040 doi:103389/fimmu201600024 
  9. ^ Soudja, Saïdi M’Homa; Chandrabos, Ceena; Yakob, Ernest; Veenstra, Mike; Palliser, Deborah; Lauvau, Grégoire 2014-06-19 "Memory-T-Cell-Derived Interferon-γ Instructs Potent Innate Cell Activation for Protective Immunity" Immunity 40 6: 974–988 ISSN 1074-7613 PMC 4105986  PMID 24931122 doi:101016/jimmuni201405005 
  10. ^ Harding, Clifford V; Boom, W Henry "Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors" Nature Reviews Microbiology 8 4: 296–307 PMC 3037727  PMID 20234378 doi:101038/nrmicro2321 
  11. ^ Dalod, M; Chelbi, R; Malissen, B; Lawrence, T 2014-05-16 "Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming" The EMBO Journal 33 10: 1104–1116 PMC 4193918  PMID 24737868 doi:101002/embj201488027 
  12. ^ Crispe, Ian N 2014-01-01 "APC licensing and CD4+T cell help in liver-stage malaria" Microbial Immunology 5: 617 PMC 4227505  PMID 25426113 doi:103389/fmicb201400617 
  13. ^ Sadegh-Nasseri, Scheherazade; Chou, Chih-Ling; Hartman, Isamu Z; Kim, AeRyon; Narayan, Kedar 2012-01-01 "How HLA-DM works: recognition of MHC II conformational heterogeneity" Frontiers in Bioscience Scholar Edition 4: 1325–1332 ISSN 1945-0524 PMID 22652874 
  14. ^ Butler, Marcus O; Hirano, Naoto 2014-01-01 "Human cell-based artificial antigen-presenting cells for cancer immunotherapy" Immunological Reviews 257 1: 191–209 ISSN 1600-065X PMC 3869003  PMID 24329798 doi:101111/imr12129 
  15. ^ Eggermont, Loek J; Paulis, Leonie E; Tel, Jurjen; Figdor, Carl G 2014-09-01 "Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells" Trends in Biotechnology 32 9: 456–465 ISSN 0167-7799 PMC 4154451  PMID 24998519 doi:101016/jtibtech201406007 
  • T J Kindt and R A Goldsby, Kuby immunology, 6th edition, WH Freeman, 2007

External linksedit

  • Antigen: protease degradation on YouTube – PMAP animation
  • Antigen-Presenting Cells at the US National Library of Medicine Medical Subject Headings MeSH


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