Describe in chronological order the steps of the antigen-processing and antigen-presentation pathways for intracellular, cytosolic pathogens

Question

What will be an ideal response?

Answer 1

Proteins derived from pathogens located in the cytosol are broken down into small peptide fragments in proteasomes. The peptides are transported into the lumen of the endoplasmic reticulum (ER) using the transporter associated with antigen processing (TAP), which is a heterodimer of TAP-1 and TAP-2 proteins anchored in the ER membrane. Meanwhile, MHC class I molecules are assembling and folding in the ER with the assistance of other proteins. Initially, the MHC class I ? chain binds calnexin through an asparagine-linked oligosaccharide on the ?1 domain. After folding and forming its disulfide bonds, the ? chain binds to ?2-microglobulin, forming the MHC class I heterodimer. At this stage, calnexin is released and the heterodimer joins the peptide-loading complex composed of tapasin, calreticulin, and ERp57, which position the heterodimer near TAP, stabilize the peptide-loading complex, and render the heterodimer in an open conformation until a high-affinity peptide binds to the heterodimer through a process known as peptide editing. The heterodimer consequently changes its conformation, is released from the peptide-loading complex, and leaves the ER as a vesicle. Arrival at the Golgi apparatus induces final glycosylation, and finally the peptide:MHC class I heterodimer complex is transported in vesicles to the plasma membrane, where it presents peptide to CD8 T cells.