DefinitionThis section has been translated automatically.
During antigen presentation, the body's own and foreign molecules (antigens) are loaded onto specialized protein complexes and thus made recognizable to certain immune cells. Antigen presentation takes different routes, which are defined by the type of antigen presented (peptide structure or lipids), the origin of the antigen (intra- or extracellular) and by the identity of the presenting complex = major histocompatibility complex (MHC) class I, major histocompatibility complex (MHC) class II or by CD1 peptides.
General informationThis section has been translated automatically.
Exogenous proteins are taken up by antigen-presenting cells (APC) through various processes (phagocytosis, endocytosis or macropinocytosis) by the cell concerned into organelles (phagosomes, endosomes, macropinosomes). These organelles fuse with the enzyme-rich lysosomes and with each other. In these organelles the proteolytic decomposition of the proteins into peptides takes place. The peptides thus processed join with the MHC protein to form an MHC-peptide complex. This is then transported to the cell surface where it is recognised by the specific TCR complex of CD4-positive lymphocytes. A "recycling pathway" then allows the MHC-II molecules to be unloaded or reloaded with peptides.
MHC-I presentation route
Cytosolic proteins of endogenous, viral or microbial origin are broken down by the proteasome into peptide fragments. Microbial proteins originate from phagosomes, where they were taken up and from where they can enter the cytosol. The proteasome, a cylindrical protein complex, is the central switch point of protein degradation. The proteasome breaks down unfolded proteins into peptide fragments using ATP-dependent proteolysis. After the peptides have left the proteasome, they bind to a heterodimeric transporter complex called TAP (transporters of antigen processing). TAP transports the complex to the endoplasmic reticulum (ER). TAP combines with the chaperones tapasin, calreticulin, calnexin and ERp57 to form the so-called "peptide loading complex" (PLC). This complex stabilises the MHC-I protein and subsequently enables its loading with peptides. The MHC-I peptide complex traverses the Golgi apparatus and is then transported to the cell surface where it is recognized by the specific receptor CD8 of positive cytotoxic T lymphocytes.
Dendritic cells, macrophages and B-lymphocytes act as antigen-presenting cells (APC). The type of APCs with which a helper cell comes into contact significantly determines its functional differentiation into TH1, TH0 or TH2 cells.
CD1 presentation pathway
In contrast to peptide antigens, lipid antigens (e.g. fatty acids, glycerol esters, sphingolipids) are not recognized in conjunction with the major histocompatibility complex - MHC, but by the CD1 complex formed by certain T cells. The CD1-complex is of special importance in the skin, as CD1 molecules are mainly formed by antigen-presenting cells, APCs of the skin. Endogenous lipids with higher affinity to the binding pocket than the protective lipid bind to the binding pocket. Similar to MHC-I, the lipid-CD1 complex is transported to the cell membrane via transport vesicles and exocyted there. Cell-membrane-bound complexes of endogenous lipid and CD1 are enclosed (endocytosed) in membrane vesicles by the antigen-presenting cell; the membrane vesicles fuse with the phagolysosomes. Exogenous lipid antigens in phagolysosomes, which have a greater affinity for the binding pocket of the CD1 molecule than the endogenous lipid located in the binding pocket, displace the latter from the binding pocket. The new lipid-CD1 complex is presented by exocytosis on the surface of the APC.
Exogenous lipid antigens are absorbed into the cell via lipid receptors by phagocytosis or endocytosis. After loading the CD1 molecules with new lipid antigens, the newly formed complexes are presented on the cell surface. In contrast to the conventional way of antigen presentation of peptides by gene products of the major histocompatibility family, the players in CD1 antigen presentation were unknown so far. Recently, it was recognized that the proteins saposin-C (SAP-C) and saposin-A play an important role in the processing of lipid antigens. Both saposins are able to transfer lipids (e.g. lipids from a bacterial membrane) to the CD1 molecule so that they can be presented as antigens.