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©2013 UpToDate ® Print Email Degradation and transport of antigens The process of degradation of proteins into peptides, transport to the endoplasmic reticulum, binding of antigenic peptides to major histocompatibility (MHC) class I molecules, presentation of antigen to a CD8 + T cell, followed by intracellular signalling (steps a-l): (a) In an antigen-presenting cell (APC), newly sythesized MHC class I molecules bind to calnexin (Cx), which retains them in a partially folded state in the endoplasmic reticulum (ER). (b) Binding of MHC class I molecules to ß2 microglobulin (ß2m) displaces Cx and allows binding of chaperonin proteins (calreticulin and tapasin; not shown). (c) The MHC class I-ß2m 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-ß2m 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 T-cell receptor (TCR) of an antigen-specific (CD8*, CD3*) cytotoxic T lymphocyte (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). Reproduced with permission from: Man, S. Human cellular immune responses against human papillomaviruses in cervical neoplasia. Exp Rev Mol Med, Cambridge University Press 1998. Reprinted with permission of Cambridge University Press