出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/31 15:36:24」(JST)
An antigen-presenting cell (APC) or accessory cell is a cell that displays foreign antigens complexed with major histocompatibility complexes (MHC's) on their surfaces. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process antigens and present them to T-cells.
APCs fall into two categories: professional or non-professional.
T cells cannot recognize, and therefore cannot respond to, 'free' antigen. T cells can only 'see' an antigen that has been processed and presented by cells via carrier molecules like MHC and CD1 molecules. 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 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, respectively. (Almost all nucleated cells express MHC class I receptors, including professional APCs. If a virus infects a macrophage or dendritic cell, it will try to promote its own destruction through cytotoxic T cells. However, dendritic cells can ingest viruses through pinocytosis and therefore activate the adaptive immune response to create antibodies for the virus through class II MHC receptors.)
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 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. The expression of co-stimulatory molecules is a defining feature of professional APCs.
There are three main types of professional antigen-presenting cell:
A non-professional APC does not constitutively express the Major Histocompatibility Complex class II (MHC class II) 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:
After APCs have phagocytosed pathogens, they usually migrate to the vast networks of lymph vessels and are carried via lymph flow to the 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 (DCs) can interact with T cells. They do this by chemotaxis, which involves interacting with chemokines that are expressed on the surface of cells (e.g., 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, it seems 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.
CD11b+CD11c+ antigen presenting cells (APC) are leukocytes that play a key role in the modulation of aortic atherosclerosis via interactions with CD4+ T-cells.[1] Atherosclerosis, a chronic inflammatory disease that causes leukocytes and plaque to build up in arterial walls, contributes greatly to the development of acute coronary syndromes.[2] The accumulation of atherosclerotic lesions progressively narrows the arteries feeding the heart and may result in ischemic myocardial damage. Knocking out co-stimulatory molecules by transgenesis on CD11b+CD11c+ APCs shows promise in its ability to protect against the debilitating effects of atherosclerosis.[1]
CD11b+CD11c+ APCs are cells that take up foreign extracellular molecules and present them to helper T-cells in order to initiate an adaptive immune response.[1] When this is done in the aorta it may lead to atherosclerosis.[1] The high surface expression of MHCII and the co-stimulatory molecules CD80 and CD86 on CD11b+CD11c+ APCs help classify them as specialized and mature APCs.[1] Additionally, these APCs also express F4/80 on their surface meaning that they consist of populations of both macrophages and dendritic cells.[1] Knocking out CD80 and CD86 decreases the activity of CD11b+CD11c+ APCs and reduces the formation of atherosclerosis.[1]
During the progression of aortic atherosclerosis the number of CD11b+CD11c+ APCs increases significantly.[1] These cells then take up residence both in the plaque and adventitia, receiving cues from cytokines to become CD11b+CD11c+ foam cells, which contribute to arterial plaque development.[1] CD11b+CD11c+ APCs take up the molecules oxidized LDL, HSP60 or ApoB100, and present them via MHCII as auto-antigens to CD4+ T-cells.[3] This in turn leads to T-cell proliferation and production of the proinflammatory cytokines IFN-γ and TNF-α in the aorta.[1]
IFN-γ and TNF-α elicit a variety of general responses in aortic atherosclerosis such as the maturation of foam cells and chemokine production, leading to the recruitment of other leukocytes.[1] More specifically, IFN-γ increases the expression of CXCL16, which is one of the receptors for oxidized LDL on macrophages in atherosclerotic lesions.[1] This in turn leads to an increase in oxidized LDL uptake and presentation by CD11b+CD11c+ macrophages to CD4+ T-cells.[1]
Normally, APCs present antigens to T-cells in lymphoid organs; however, atherosclerotic lesions do not have lymph vessels meaning that CD11b+CD11c+ APCs cannot reach the lymphoid organs.[1] CD11b+CD11c+ APCs and CD4+ T-cells must rely on local communication for atherosclerotic progression.[1] Since APCs are localized in the aorta and do not travel to lymph nodes, CD4+ T-cells undergo antigen-dependent reactivation and sustained proinflammatory cytokine release, which continues macrophage conversion and atherosclerosis progression.[1]
Kindt, TJ & Goldsby, RA, 2007, Kuby immunology, 6th ed, W.H. Freeman, New York, N.Y.
|
||||||||||||||||||||||||||||||||||
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
| リンク元 | 「抗原提示細胞」「APC」 |
| 拡張検索 | 「professional antigen-presenting cell」「antigen-presenting cells」 |
| 関連記事 | 「cell」 |