Antigen presentation

When antigen presentation endogenous and foreign molecules (antigens ) are loaded on specialized protein complexes and thus made visible for certain immune cells. Antigen presentation via different mechanisms that differ in the nature of the presented antigen (peptide or lipid), the origin of the antigen ( intra-or extracellular) and the identity of presenting complex ( major histocompatibility complex ( MHC) class I or class II).

MHC I

MHC I is required for the presentation of intracellular antigens. It is expressed by all nucleated cells. Erythrocytes, for example, have on their cell surface MHC I. Cytosolic proteins not, whether endogenous or exogenous, (peptides ) are in the proteasome into small protein fragments. These peptides have certain characteristics ( basic and hydrophobic residues) and specifically from the transporter TAP ( transporter associated with antigen processing engl. ) in the endoplasmic reticulum ( ER) transported. Inside the ER, MHC -I is brought into the vicinity of the local means of the TAP adapter protein tapasin. The imported by TAP peptide will be preferentially bound to these MHC -I. Only then is the MHC I is transported to the cell surface. MHC I therefore presented either endogenous antigens or those derived from viruses that reside in the cytosol of cells, and synthesize their own proteins. MHC class I presented peptide antigen to CD8 T lymphocytes. In this cellular contact between an antigen presenting cell (APC ) and a CD8 T lymphocytes leads to the formation of a receptor - compaction (so-called immunological synapse ), the quite essential for the activation of CD8 T - cell to cytotoxic T lymphocytes ( CTL) contributes. A once activated CTL can recognize MHC class I on the surface of nucleated cells in the body in its turn, once these (eg a virus protein) present the peptide to the CTL was activated. As a result, the virus- infected cell is killed by the CTL, a process that is called cell-mediated cytotoxicity.

MHC II

MHC II is used for the presentation of extracellular antigens. MHC class II is expressed only by certain cells, such as dendritic cells. The peptide - binding pocket of the complex - as long as it is in the ER - by an invariant chain, also a peptide blocked. Until the fusion of the vesicle with a MHC -bearing phagolysosome and the presence of HLA -DM, and the acidic pH environment displace the invariant chain of the peptide - binding pocket, and allow the binding of another peptide. This peptide is extracellular origin. There was an organism (e.g. a bacterium) absorbed by phagocytosis, for example, a dendritic cell (as well as macrophages and B cells) and decomposed in the phagolysosome into fragments. This shows the completely different origin of the peptide fragments that are presented on MHC -II. Dendritic cells presenting MHC -II Peptifragmente the CD4 T lymphocytes. The CD4 T cell can now turn activate B cells for antibody production or cause macrophages to destroy the phagocytosed pathogens in the phagolysosome. All of these cell-cell contacts show the same characteristic structure, which is referred to as immunological synapse.

Be ensured both in antigen presentation via MHC -I and MHC - II must demonstrate that the presented peptide does not dissolve during the stay on the cell membrane and in the worst case replaced by another fragment. These non-covalent binding between MHC and peptide is characterized by a slow on / off rate. This means on the one hand, that the binding in the endoplasmic reticulum takes a long time ( on- rate ), but once bound peptides can then also for a very long time are presented very stable (over days) (off - rate). Another safety device is the stability of the MHC. Without bound peptide disintegrates the whole complex and is internalized by the cell via endocytosis immediately.

The MHC molecules are called human HLA ( human leucocyte antigens engl. ). This corresponds to the MHC-I: HLA- A, B, C, and MHC -II: HLA- DR, HLA-DQ and HLA- DP. Certain HLA genes associated with the development of autoimmune diseases such as ankylosing spondylitis, lupus erythematosus (SLE ), insulin - dependent diabetes mellitus ( IDDM ) and much more.

Cross-presentation

The cross-presentation combines the features of the above classic presentation pathways, ie there are antigens or proteins from the extracellular space was added, the resulting continuous antigenic peptides presented on MHC -I, however, complexes to 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, the cross-presentation of great importance in the maintenance of self- tolerance to endogenous proteins.

The cross-presentation was detected predominantly in dendritic cells, which receive the extracellular proteins either by phagocytosis of dead cells by specific receptors or by pinocytosis of tissue fluid. The loading of MHC -I complexes are composed of TAP, but the exact mechanism is not yet finally resolved.

This form of antigen presentation is probably important when pathogens especially non-immune cells affected, because this alone is unlikely to be able to elicit an effective immune response in itself. However, the transfer of the antigen on dendritic cells and the subsequent cross-presentation allow the activation of CD8 T lymphocytes, which play a crucial role especially in the defense against intracellular pathogens.

CD1

CD1 is an MHC - I- like molecule. In the human genome, there are five isoforms. While MHC I and II are, however, limited to the presentation of peptides, CD1 molecules present mainly lipids. These may have their origin in apoptosis vesicles. Apoptotic vesicles are formed, for example, in the demise of macrophages infected by Mycobacterium tuberculosis infection. Dendritic cells take up and present these Apoptosevesikel therein lipid antigens to T cells in draining lymph nodes. This way of antigen presentation is called the detour pathway Upon processing of the lipid antigens, especially the protein saposin C ( SAP -C ) plays an important role, since it is capable of transferring lipids from a membrane on CD1. CD1d is recognized by NKT cells as a ligand. NKT cells are a subpopulation of T cells; they were first described as T- cells having markers of NK cells ( CD161 in humans). Unlike conventional T cells to secrete large amounts of cytokines of TH1 and TH2 - type (such as interferon γ, interleukin -4). The CD1d surface expression can be modulated by cytokines. Research with CD1d to new ways of antigen recognition, Tumorimunologie and therapeutic approaches.