Antigen presentation
| Parent |
| Process of the immune system |
| Subordinate |
| Antigen presentation in B / T / dendritic cells / monocytes / macrophages Presentation of exogenous / endogenous / peptide antigens Antigen presentation after receptor-controlled uptake / pinocytosis / phagocytosis via MHC IB / II |
| Gene Ontology |
|---|
| QuickGO |
During the antigen presentation , the body's own and foreign molecules ( antigens ) are loaded onto specialized protein complexes and thus made visible to certain immune cells . Antigen presentation takes place via different mechanisms that differ in the type of antigen presented ( peptide or lipid ), the origin of the antigen (intra- or extracellular) and the identity of the presenting complex ( main histocompatibility complex (MHC) class I or class II).
MHC I
MHC I is used to present intracellular antigens. It is used by all nucleated cells (with the exception of trophoblasts ). Erythrocytes e.g. B. have no MHC I on their cell surface. Cytosolic proteins , whether endogenous or foreign, are broken down into small protein fragments ( peptides ) in the proteasome . These peptides have certain properties (basic and hydrophobic residues) and are specifically transported by the transporter TAP ( transporter associated with antigen processing ) into the endoplasmic reticulum (ER). Inside the ER, the MHC-I is brought into close proximity to the TAP by means of the adapter protein tapasin . The peptide imported by TAP is now preferentially bound to this MHC-I. Only then is the MHC-I transported to the cell surface. MHC I therefore presents either the body's own antigens or those that come from viruses that reside in the cytosol of the cells and synthesize their own proteins. MHC I presents the antigen peptide to CD8 + T lymphocytes . This cellular contact between an antigen-presenting cell (APC) and a CD8 + T lymphocyte leads to the formation of a receptor compression (so-called immunological synapse ), which is essential for the activation of the CD8 + T cell to become cytotoxic T lymphocytes ( CTL) contributes. A once activated CTL can in turn recognize MHC I on the surface of nucleated body cells as soon as these present the peptide (e.g. from a virus protein or a tumor-associated antigen ) with which the CTL was activated. As a result, the virus-infected or degenerate cell is killed by the CTL, a process called cell-mediated cytotoxicity .
MHC II
MHC II is used to present extracellular antigens. MHC II is only used by certain cells, e.g. B. by dendritic cells expressed. The peptide binding pocket of this complex is - as long as it is in the ER - blocked by an invariant chain , also a peptide. Only the fusion of the MHC-bearing vesicle with a phagolysosome and the presence of HLA-DM as well as the acidic pH environment displace the invariant chain from the peptide binding pocket and enable the binding of another peptide. This peptide is of extracellular origin. There an organism (e.g. a bacterium) was phagocytosed e.g. B. taken up by a dendritic cell (but also by macrophages and B cells) and broken down into fragments in the phagolysosome. This shows the completely different origin of the peptide fragments presented on MHC-II. Dendritic cells present the peptide fragments to CD4 + T lymphocytes via MHC-II . The CD4 + T cell can now activate B cells to produce antibodies or induce macrophages to destroy the phagocytosed pathogens in the phagolysosome . All of these cell-cell contacts show the same characteristic structure, which is called the immunological synapse .
In the case of antigen presentation via MHC-I as well as via MHC-II, it must be ensured that the peptide presented does not dissolve while it is on the cell membrane and, in the worst case, is replaced by another fragment. This non-covalent bond between MHC and peptide is characterized by a slow on / off rate. On the one hand, this means that the binding in the endoplasmic reticulum takes a very long time (on-rate), but once bound peptides can then also be presented in a very stable manner for a very long time (over days) (off-rate). Another safety feature is the stability of the MHC. Without a bound peptide, the whole complex disintegrates and is immediately internalized by the cell via endocytosis.
The MHC molecules are called HLA ( human leucocyte antigens ) in humans . The MHC-I: HLA-A, B, C and the MHC-II: HLA-DR, HLA-DQ and HLA-DP. Certain HLA genes are linked to the development of autoimmune diseases such as ankylosing spondylitis , lupus erythematosus (SLE), insulin-dependent diabetes mellitus (IDDM) and many more.
Cross presentation
The cross presentation combines properties of the above-mentioned classic presentation methods, i. H. antigens or proteins are taken up from the extracellular space, but the resulting antigenic peptides are presented on MHC-I complexes on CD8 + -cytotoxic T cells . This molecular and cell biological mechanism plays a central role in the activation of cytotoxic T lymphocytes against virus- infected or neoplastic cells (tumors). In addition, cross-presentation is of great importance in maintaining self-tolerance towards the body's own proteins.
The cross-presentation was proven mainly in dendritic cells, which take up the extracellular proteins either through phagocytosis of dead cells, through special receptors or through pinocytosis of tissue fluid. The MHC-I complexes are loaded with the assistance of the TAP, but the exact mechanism has not yet been finally clarified.
This form of antigen presentation is presumably important when pathogens primarily attack non-immune cells, as these can hardly trigger an effective immune response on their own. However, the transfer of the antigen to dendritic cells and the subsequent cross-presentation enable the activation of CD8 + T lymphocytes, which play a particularly important role in the defense against intracellular pathogens.
CD1
CD1 is an MHC-I-like molecule. There are five isoforms in the human genome. However, while MHC I and II are limited to the presentation of peptides, CD1 molecules mainly present lipids. These can originate in apoptosis vesicles. Apoptosis vesicles arise z. B. the death of macrophages that are infected by an infection with Mycobacterium tuberculosis . Dendritic cells take up these apoptosis vesicles and present the lipid antigens they contain to T cells in a draining lymph node. This way of antigen presentation is called the detour pathway . The protein saposin-C (SAP-C) in particular plays an important role in the processing of lipid antigens, as it is capable of transferring lipids from a membrane to CD1. CD1d is recognized as a ligand by NKT cells. NKT cells represent a subpopulation of T cells. They were first described as T cells with markers from NK cells (CD161 in humans). In contrast to conventional T cells, they secrete large amounts of cytokines of the TH1 and TH2 types (including interferon γ , interleukin-4 ). CD1d surface expression can be modulated by cytokines. Research with CD1d should reveal new ways of antigen recognition, tumor immunology and therapeutic approaches.
Individual evidence
- ^ JA Villadangos, WR Heath, FR Carbone: Outside looking in: the inner workings of the cross-presentation pathway within dendritic cells. In: Trends in Immunology . Volume 28, Number 2, February 2007, pp. 45-47, ISSN 1471-4906 . doi: 10.1016 / j.it.2006.12.008 . PMID 17197240 .
- ↑ C. Kurts et al .: Constitutive class I-restricted exogenous presentation of self antigens in vivo . In: J Exp Med . tape 184 , no. 3 , 1996, p. 923-930 , PMID 9064352 .
- ↑ JM den Haan et al .: CD8 (+) but not CD8 (-) dendritic cells cross-prime cytotoxic T cells in vivo . In: J Exp Med. Band 192 , no. 12 , 2000, pp. 1685-1696 , PMID 11120766 .