
Processing and presentation of intracellular antigens - The ER-MHC class I pathway

Now that we know what the purpose of processing and presentation is, we can look at the mechanisms more closely...
Intracellular antigens tend to be self proteins, newly synthesised viral proteins or protein from ingested microbes that have been transported to the cytosol, and are not generally processed into peptides in the endosomal compartments like extracellular antigens. Instead they are degraded via the proteasome to generate peptides that can associate with MHC class I. Let's have a look at this video which illustrates how this happens. While you are watching try to spot how small peptides are obtained from larger proteins and which molecule loads these peptides onto the MHC I complex.
As you could see, the proteasome is a large multi-protein enzyme complex that, in addition to generating the peptides, also directs them into the endoplasmic reticulum (ER) with the help of specialised transporters, where the loading of the peptides on to the forming MHC class I takes place. The ER is a series of tubules and vesicles within the cytoplasm that, in broad terms, are responsible for the synthesis of proteins (rough ER), lipids and steroids (smooth ER). Did you also notice that MHC class I molecules recognise specific peptides? What was the name of the process that determines which peptides bind to MHC class I? If you missed it, why not have a second look at the video?