Degradation and transport of antigens

The process of degradation of proteins into peptides, transport to the endoplasmic reticulum, binding of antigenic peptides to MHC class I molecules, presentation of antigen to a CD8+ T cell, followed by intracellular signaling (steps a-l): (a) In an APC, newly synthesized MHC class I molecules bind to calnexin, which retains them in a partially folded state in the ER. (b) Binding of MHC class I molecules to beta-2m displaces calnexin and allows binding of chaperonin proteins (calreticulin and tapasin; not shown). (c) The MHC-class-I-beta-2m complex binds to the TAP complex (TAP1-TAP2), which awaits the delivery of peptides. (d) Peptides (eg, from antigens) are formed from the degradation of cytosolic proteins (self-, pathogen-, and tumor-derived proteins in the cytoplasm). (e) These are degraded by proleasomes into (f) short peptides. (g) Peptides are transported into the ER by the TAPs, where they meet the MHC-class-I-beta-2m complex (h). This peptide binding in the antigenic groove of the MHC stabilizes the structure of the MHC class I molecule and (i) releases the TAP complex. (j) The fully folded MHC class I molecule with its peptide is transported to the cell surface via the Golgi apparatus. (k) Recognition of the MHC class I-peptide complex by the TCR of an antigen-specific (CD8*, CD3*) CTL takes place and (l) a signal transduction event activates effector functions in the MHC-class-I-restricted T cell; this requires co-simulation to occur (not shown).