Antigen processing and presentation

The majority of antigens presented by MHC class I molecules are generated in the cytosol after proteolysis of endogenous proteins by proteasomes. Short peptides are then transferred into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP), and after binding to newly assembled MHC class I molecules, are transported to the plasma membrane. Similar to MHC class I, class II molecules assemble in the ER. However, class II molcules bind antigenic peptides in endosomal structures. MHC class II antigen processing and presentation can be blocked by reagents that raise endosomal pH (such as ammonium chloride, concana-mycin A or chloroquine). In the ER, MHC class II molecules associate with the invariant chain (Ii); this association is required for efficient release of MHC,' class II from the ER. The signals that target the class II—Ii complex to the endosomal compartment are located in the cytoplasmic tail of Ii. Upon arrival in the endosomes, Ii is degraded, allowing the peptide-binding groove of MHC class II to be exposed for loading of the antigenic peptide. Two MHC class II-like structures, HLA-DMA and HLA-DMB, play an essential supporting role in processing of antigens presented by MHC class II molecules. Class II molecules on cells with specific deletions in HLA-DM

CD1 MHC MHC

class I class II

Figure 2 A proposed domain organization of CD1 proteins in comparison to MHC class I and II proteins. , /V-linked glycosylate; C1, immunoglobulin C1 -like domain; S- S, intradomain disulfide bonds. (Reproduced with permission from Porcelli (1995).)

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